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The Role of Estrogen in Breast Cancer

  • Chapter
Molecular Basis of Breast Cancer

Abstract

Intensive epidemiological studies have identified a number of genetic risk factors associated with breast cancer, including evidence of BRCA1 and BRCA2 susceptibility genes, familiar history of cancer in the breast, ovary or endometrium and individual history of breast diseases [1]. An increased risk has also been associated with early onset of menstruation, nulliparity or delayed first childbirth, short duration of breast feeding, late menopause, use of hormone replacement therapy and increased bone density [2–4]. A principal culprit common for all these endocrine-related risk factors is the prolonged exposure to female sex hormones [5–8]. The hormonal influences have been mainly attributed to unopposed exposure to elevated levels of estrogens [5], as has been indicated for a variety of female cancers, namely, vaginal, hepatic and cervical carcinomas [9–11]. Exposure to estrogens, particularly during the critical developmental periods (e.g., in utero, puberty, pregnancy, menopause), also affects affective behaviors (e.g., depression, aggression, alcohol intake) and increases breast cancer risk [12].

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References

  1. Landis, S.H., Murray, T., Bolden, S., Wingo, P.A. CA Cancer J. Clin. 49:8, 1999.

    PubMed  CAS  Google Scholar 

  2. Pike, M.C. Spicer, D.V., Dahmoush, L. Press, M.F. Estrogens, progesterone, normal breast cell proliferation and breast cancer risk, Epidemiol. Rev. 15:17–35, 1993.

    PubMed  CAS  Google Scholar 

  3. Kelsey, J.L., Gammon, M.D., John, E.M. Reproductive factors and breast cancer, Epidemiol. Rev. 15:36–47, 1993.

    PubMed  CAS  Google Scholar 

  4. Bernstein, L., Ross, R.K. Endogenous hormones and breast cancer risk, Epidemiol. Rev. 15:48–65, 1993.

    PubMed  CAS  Google Scholar 

  5. Henderson, B.E., Ross, R., Bernstein, L. Estrogens as a cause of human cancer: the Richard, Estrogens as a cause of human cancer: the Richard & Hinda Rosenthal Foundation Award Lecture, Cancer Res. 48:246–253, 1988.

    PubMed  CAS  Google Scholar 

  6. Topper, Y.J., Sankaran, L., Chomczynski, P., Prosser, P., Qasba, P. Three stages of responsiveness to hormones in the mammary cell, In: A. Angeli, H.L. Bradlow, L. Dogliotti (Eds.), Endocrinology of the Breast: Basic and Clinical Aspects, Ann. New York Acad. Sci. 464:1–10, 1986.

    Google Scholar 

  7. Lippman, M.E., Huff, K.K., Jakesz, R., Hecht, T., Kasid, A., Bates, S., Dickson, R.B. Estrogens regulate production of specific growth factors in hormone-dependent human breast cancer, In: A. Angeli, H.L., Bradlow, L. Dogliotti (Eds.), Endocrinology of the Breast: Basic and Clinical Aspects, Ann. New York Acad. Sci. 464:11–6, 1986.

    Google Scholar 

  8. Dupont, W.D., Page, D.L. Menopausal estrogen replacement therapy and breast cancer. Arch. Int. Med. 151:67–72, 1991.

    CAS  Google Scholar 

  9. Toniolo, P.G. Endogenous estrogens and breast cancer risk: the case for prospective cohort studies. Environ Health Perspect. 105 Suppl 3:587–92, 1997

    PubMed  Google Scholar 

  10. Greenwald, P., Barolom, J., Nasca, P., Burnett, W. Vaginal cancer after maternal treatment with synthetic estrogens. N. Engl. J. Med. 12:285(7): 390–240, 1971.

    Google Scholar 

  11. Beral, V., Hannaford, P., Kay, C. Oral contraceptive use and malignancies of the genital tract. Results from the Royal College of General Practitioners' Oral Contraception Study. Lancet 2:1331–1335, 1988.

    PubMed  CAS  Google Scholar 

  12. Hilakivi-Clarke, L. Estrogen-regulated non-reproductive behaviors and breast cancer risk: animal models and human studies. Breast Cancer Res. Treat. 46:143, 1997.

    PubMed  CAS  Google Scholar 

  13. Davis, D.L., Telang, N.T., Osborne, M.P., Bradlow, H.I. Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer. Environ Health Perspect. 105 suppl 3:571–576, 1997.

    PubMed  CAS  Google Scholar 

  14. Sonnenschein, C., Soto, A.M. An updated review of environmental estrogen and androgen mimics and antagonists. J. Steroid Biochem. Mol. Biol. 65:143–150, 1998.

    PubMed  CAS  Google Scholar 

  15. Price, M.A., Tennant, C.C., Smith, R.C., Kennedy, S.J., Butow, P.N., Kossoff, M.B., Dunn, S.M. Predictors of breast cancer in women recall following screening, Aust. New Zealand J. Surg. 69:639–646, 1999.

    CAS  Google Scholar 

  16. Couse, J.R, Korach, K.S. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr. Rev. 20:358–417, 1999.

    PubMed  CAS  Google Scholar 

  17. Shiau, A.K., Barstad, D., Loria, P.M., Cheng, L., Kushner, P.J., Agard, D.A., Greene, G.L. The structural basis of estrogen receptor/ coactivator recognition and the antagonism of this interaction by tamoxifen. Cell 95:927–937, 1998.

    PubMed  CAS  Google Scholar 

  18. McDonnell, D.P. The molecular pharmacology of SERMs. TEM 10:301–311, 1999.

    PubMed  CAS  Google Scholar 

  19. Tsai, M.J., O’Malley, B.W. Molecular mechanisms of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63:451–486, 1994.

    PubMed  CAS  Google Scholar 

  20. Katzenellenbogen, B.S. Dynamics of steroid hormone receptor action, Annu. Rev. Physiol. 42:17–35, 1980.

    PubMed  CAS  Google Scholar 

  21. Mosselman, S., Polma, J., Dijkema, R. ER-: identification and characterization of a novel human estrogen receptor, FEBS Lett. 392:49–53, 1996.

    PubMed  CAS  Google Scholar 

  22. Kuiper, G.G.J.M., Carlsson, B., Grandien, K., Enmark, E., et al., Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors or and, Endocrinology 138:863–870, 1997.

    PubMed  CAS  Google Scholar 

  23. Paech, K., Webb, P., Kuiper, G.G., Nilsson, S., Gustatsson, J., Kushner, P.J., Scanlan, T.S. Differential ligand activation of estrogen receptors ER-alpha and ER-beta at API sites, Science 277:150:8–1510, 1997.

    CAS  Google Scholar 

  24. Rao, B.R. Isolation and characterization of an estrogen binding protein which may integrate the plethora of estrogenic actions in non-reproductive organs J. Steroid Biochem. Mol. Biol. 65:3–41, 1998.

    CAS  Google Scholar 

  25. Bhat, R.A., Harnish, D.C., Stevis, P.E., Lyttle, C.R., Komm, B.S. A novel human estrogen receptor beta: identification and functional analysis of additional N-terminal amino acids. J. Steroid Biochem. Mol. Biol. 67:233–240, 1998.

    PubMed  CAS  Google Scholar 

  26. Hu, Y-E, Russo, I.H., and Russo, J. Estrogen and Human Breast Cancer. In: Endocrine disruptors (M. Matzler Ed.) Springer Verlag, Heidelberg 2001 pp 1–26.

    Google Scholar 

  27. van Landeghem, A.A.J., Poortman, J., Nabuurs, M., Thijssen, J.H.H. Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res. 45:2900–2906, 1985.

    PubMed  Google Scholar 

  28. Labrie, E Intracrinology, Mol. Cell Endocrinol. 78:C113–118, 1991.

    PubMed  CAS  Google Scholar 

  29. Labrie, E, Simard, J., Luu-The, V., Pelletier, G., Belghmi, K., Belanger, A. Structure, regulation and role of 3 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase and aromatase enzymes in the formation of sex steroids in classical and peripheral intracrine tissues. Bailliere’s Clin. Endocrinol. Metab. 8:451–474, 1994.

    CAS  Google Scholar 

  30. Pasqualini, J.R., Chetrite, G., Nguyen, B.L., Maloche, C., Talbi, M., Feinstein, M.C., Blacker, C., Botella, J., Paris, J. Estrone sulfate-sulfatase and 17 beta-hydroxysteroid dehydrogenase activities: a hypothesis for their role in the evolution of human breast cancer from hormone-dependence to hormone-independence. J. Steroid. Biochem. Mol. Biol. 53:407–412, 1995.

    PubMed  CAS  Google Scholar 

  31. Reed, M.J., Purohit, A. Breast cancer and the role of cytokines in regulating estrogen synthesis: An emerging hypothesis. Endocrine Review 18,701–715, 1997.

    CAS  Google Scholar 

  32. Simpson, E.R., Mahendroo, M.S., Means, G.D., Kilgore, M.W., Hinshelwood, M.M., Graham-Lorence, S., Amarneh, B., Ito, Y., Fisher, C.R., Michael, M.D. et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocrine Rev. 15:342–355, 1994.

    CAS  Google Scholar 

  33. Santen, R.J., Santner, S.J., Pauley, R.J., Tait, L., Kaseta, J., Demers, L.M., Hamilton, C., Yue, W., Wang, J.P. Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible? J. Steroid Biochem. Mol. Biol. 61:267–271, 1997.

    PubMed  CAS  Google Scholar 

  34. Brodie, A., Lu, Q., Nakamura, J. Aromatase in the normal breast and breast cancer. J. Steroid Biochem. Mol. Biol. 61:281–286, 1997.

    PubMed  CAS  Google Scholar 

  35. Koh, J.I., Kubota, T., Sasano, H., Hashimotom, M., Hosoda, Y, Kitajima, M. Stimulation of human tumor xenograft growth by local estrogen biosynthesis in stromal cells. AntiCancer Res. 18:2375–2380, 1998.

    PubMed  CAS  Google Scholar 

  36. Mor, G., Yue, W, Santen, R.J., Gutierrez, L., Eliza, M., Berstein, L.M., Harada, N., Wang, J., Lysiak, J., Diano, S., Naftolin, E J. Steroid Biochem. Mol. Biol. 67:403, 1998.

    CAS  Google Scholar 

  37. Miller, W.R, O’Neill, J. The importance of local synthesis of estrogen within the breast. Steroids 50:537–548, 1987.

    PubMed  CAS  Google Scholar 

  38. Dowsett, M. Future uses for aromatase inhibitors in breast cancer. J. Steroid Biochem. Mol. Biol. 61:261–266, 1997.

    PubMed  CAS  Google Scholar 

  39. Sasano, H., Ozaki, M. Aromatase expression and its localization in human breast cancer. J. Steroid Biochem. Mol. Biol. 61:293–298, 1997.

    PubMed  CAS  Google Scholar 

  40. Orentreich, N., Brind, J.L., Rizer, R.L. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J. Clin. Endocrinol. Metab. 59:551–555, 1984.

    PubMed  CAS  Google Scholar 

  41. Falany, J.L., Falany, C.N. Regulation of estrogen activity by sulfation in human MCF-7 breast cancer cells. Oncol. Res. 9:589–596, 1997.

    PubMed  CAS  Google Scholar 

  42. Utsumi, T., Yoshimura, N., Takeuchi, S., Ando, J., Maruta, M., Maeda, K., Harada, N. Steroid sulfatase expression is an independent predictor of recurrence in human breast cancer. Cancer Res. 59:377–381, 1999.

    PubMed  CAS  Google Scholar 

  43. Martel, C., Rheaume, E., Takahashi, M., Trudel, C., Couet, J., Luu-The, V., Simard, J., Labrie, F. Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. J. Steroid Biochem. Mol. Biol. 41:597–603, 1992.

    PubMed  CAS  Google Scholar 

  44. Luu-The, V., Zhang, Y., Poirier, D., Labrie, F. Characteristics of human types 1,2 and 3 17 beta-hydroxysteroid dehydrogenase activities: oxidation/reduction and inhibition. J. Steroid Biochem. Mol. Biol. 55:581–587, 1995.

    PubMed  CAS  Google Scholar 

  45. Simard, J., Durocher, F., Mebarki, F., Turgeon, C., Sanchez, R., Labrie, Y, Couet, J., Trudel, C., Rheaume, E., Morel, Y, Luu-The, V., Labrie, F. Molecular biology and genetics of the 3 beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. J. Endocrinol. 50:189–207, 1996.

    Google Scholar 

  46. Sasano, H., Frost, A.R., Saitoh, R., Harada, N., Poutanen, M., Vihko, R., Bulun, S.E., Silverberg, S.G., Nagura, H. Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma. J. Clin. Endocr. Metab. 81:4042–4046, 1996.

    PubMed  CAS  Google Scholar 

  47. Miller, W.R., Anderson, T.J., Lack, W.J.L. Relationship between tumour aromatase activity, tumour characteristics and response to therapy. J. Steroid Biochem. Mol. Biol. 37:1055–1059, 1990.

    PubMed  CAS  Google Scholar 

  48. Esteban, J.M., Warsi, Z., Haniu, M., Hall, P., Shively, J.E., Chen, S. Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation Am. J. Pathol. 940:337–343, 1992.

    Google Scholar 

  49. Russo, J., Russo, I.H. Role of hormones in human breast development: The menopausal breast. In: Wren BG (ed) Progress in the management of menopause. Parthenon Publishing 1997 New York. P 184

    Google Scholar 

  50. Russo, I.H., Russo, J. Role of hormones in cancer initiation and progression. J. Mammary Gland Biol. Neoplasia 3:49–61, 1998.

    PubMed  CAS  Google Scholar 

  51. Russo, J., Russo, I.H. Role of differentiation in the pathogenesis and prevention of breast cancer. Endocr. Related Cancer 4:7, 1997.

    CAS  Google Scholar 

  52. Calaf, G., Alvarado, M.E., Bonney, G.E., Amfoh, K.K., Russo, J. Influence of lobular development on breast epithelial cell proliferation and steroid hormone receptor content. Int. J. Oncol. 7:1285, 1997.

    Google Scholar 

  53. Russo, J., Russo, I.H. Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis. Cancer Res. 40:2677, 1980.

    PubMed  CAS  Google Scholar 

  54. Russo, J., Russo, I.H. Biological and molecular bases of mammary carcinogenesis. Lab Invest. 57:112, 1987.

    PubMed  CAS  Google Scholar 

  55. Russo, J., Rivera, R., Russo, I.H. Influence of age and parity on the development of the human breast. Breast Cancer Res. Treat. 23:211–218, 1992.

    PubMed  CAS  Google Scholar 

  56. Russo, J., Grill, C., Ao, X., Russo, I.H. Pattern of distribution for estrogen receptor a and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res. Treat. 53:217–227, 1999.

    PubMed  CAS  Google Scholar 

  57. Clark, R.B.k, Howell, A. Potten, C.S., Anderson E., Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 57:4987–4991, 1997.

    Google Scholar 

  58. Foster, J.S., Wimalasena, J. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Mol. Endocrinol. 10:488–98, 1996.

    PubMed  CAS  Google Scholar 

  59. Wang, W, Smith, R., Burghardt, R., Safe, S.H. 17 beta-Estradiol-mediated growth inhibition of MDA-MB-468 cells stably transfected with the estrogen receptor: cell cycle effects. Mol. Cell Endocrinol. 133:49–62, 1997.

    PubMed  CAS  Google Scholar 

  60. Zajchowski, D.A., Sager, R., Webster, L. Estrogen inhibits the growth of estrogen receptor-negative, but not estrogen receptor-positive, human mammary epithelial cells expressing a recombinant estrogen receptor. Cancer Res. 53:5004–5011, 1993.

    PubMed  CAS  Google Scholar 

  61. Calaf, G., Tahin, Q., Alvarado, M.E., Estrada, S., Cox, T. and Russo, J. Hormone receptors and cathepsin D levels in human breast epithelial cells transformed by chemical carcinogens. Breast Cancer Res. and Treat. 29:169–177, 1993.

    Google Scholar 

  62. Santen, R. J. Symposium overview. J. Natl. Cancer Institute Monograph 27, 2000, pp 15–16.

    Google Scholar 

  63. Adlercreutz, H., Gorbach, S.L., Goldin, B.R., Woods, M.N., Hamalainen, E. Estrogen metabolism and excretion in Oriental and Caucasian women. J. Natl. Cancer Inst. 86:1076–1082, 1994.

    PubMed  CAS  Google Scholar 

  64. Roy, D., Liehr, J.G. Temporary decrease in renal quinone and reductase activity induced by chronic administration of estradiol to male Syrian hamsters-increased Superoxide formation by redox cycling of estrogen. J. Biol. Chem. 263:3646–3651, 1988.

    PubMed  CAS  Google Scholar 

  65. Meads, T., Schroer, T. A. Polarity and nucleation of microtubules in polarized epithelial cells. Cell Motil. Cytoskeleton, 32:273–288, 1995.

    PubMed  CAS  Google Scholar 

  66. Whitehead, C. M., Salisbury, J. L. Regulation and regulatory activities of centrosomes. J. Cell. Biochem. Suppl., 32-33: 192–199, 1999.

    Google Scholar 

  67. Sluder, G., Hinchcliffe, E H. Control of centrosome reproduction: the right number at the right time. Biol. Cell, 91:413–427, 1999.

    PubMed  CAS  Google Scholar 

  68. Pihan, G.A., Doxsey, S.J. The mitotic machinery as a source of genetic instability in cancer. Semin. Cancer Biol. 9:289–302, 1999.

    PubMed  CAS  Google Scholar 

  69. Brinkley, B.R., Goepfert, T.M. Supernumerary centrosomes and cancer: Boveri’s hypothesis resurrected. Cell Motil. Cytoskeleton, 41:281–288, 1998.

    PubMed  CAS  Google Scholar 

  70. Lingle, W.L., Lutz, W.H., Ingle, J.N., Maihle, N.J., Salisbury, J.L. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc. Natl. Acad. Sci. USA, 95:2950–2955, 1998.

    PubMed  CAS  Google Scholar 

  71. Mendelin, J., Grayson, M., Wallis, T., Visscher, D. W. Analysis of chromosome aneuploidy in breast cancer progression using fluorescence in situ hybridization. Lab. Invest. 79:387–393, 1999.

    PubMed  CAS  Google Scholar 

  72. Lengauer, C., Kinzler, K.W., Vogelstein, B. Genetic instabilities in human cancers. Nature (London) 396:643–648, 1998.

    CAS  Google Scholar 

  73. Chakravarti, D., Mailander P., Cavalieri, E.L., and Rogan, E.G. Evidence that error-prone DNA repair converts dibenzo [a,l]pyrene-induced depurinating lesions into mutations: Formation, clonal proliferation and regression of initiated cells carrying H-ras oncogene mutations in early preneoplasia. Mutation Res. 456:17–32, 2000.

    PubMed  CAS  Google Scholar 

  74. Khan, S.A., Rogers, M.A., Khurana, K.K., Meguid, M.M., Numann, P.J. Estrogen receptor expression in benign breast epithelium and breast cancer risk. J. Natl. Cancer Inst. 89:3742, 1997.

    Google Scholar 

  75. Russo, J., Reina, D., Frederick, J., Russo, I.H. Expression of phenotypical changes by human breast epithelial cells treated with carcinogens in vitro. Cancer Research, 48:2837–2857. 1988.

    PubMed  CAS  Google Scholar 

  76. Russo, J., Calaf, G., and Russo, I.H. A critical approach to the malignant transformation of human breast epithelial cells. CRC Critical Reviews in Oncogenesis 4:403–417, 1993.

    CAS  Google Scholar 

  77. Russo, J., Gusterson, B.A., Rogers, A.E., Russo, I.H., Wellings, S.R. and Van Zwieten, M.J. Comparative Study of Human and Rat Mammary Tumorigenesis. Lab. Invest. 62:1–32, 1990.

    Google Scholar 

  78. Harlan, L.C., Coates, R.J., Block, G. Estrogen receptor status and dietary intakes in breast cancer patients. Epidemiology 4:25–31, 1993.

    PubMed  CAS  Google Scholar 

  79. Habel, L.A., Stanford, J.L. Hormone receptors and breast cancer. Epidemiol. Rev. 15:209–219, 1993.

    PubMed  CAS  Google Scholar 

  80. Moolgavkar, S.H., Day, N.E., Stevens, R.G. Two-stage model for carcinogenesis: Epidemiology of breast cancer in females. J. Natl. Cancer Inst. 65:559–569, 1980.

    PubMed  CAS  Google Scholar 

  81. Hu, Y.E, Lau, K.M., Ho, S.M. and Russo, J. Increased expression of estrogen receptor beta in chemically transformed human breast epithelial cells. Int. J. Oncol. 12:1225–1228, 1998.

    PubMed  CAS  Google Scholar 

  82. Lau, K.M., Leav, I., Ho, S.M. Rat estrogen receptor a and β, and progesterone receptor mRNA expression in various prostatic lobes and microdissected normal and dysplastic epithelial tissues of the Noble rats. Endocrinology 139:424–427, 1998.

    PubMed  CAS  Google Scholar 

  83. Brandenberger, A.W., Tee, M.K., Jaffe, R.B. Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ovarian serous cystadenocarcinoma and ovarian cancer cell lines: down-regulation of ER-beta in neoplastic tissues. J. Clin. Endocrinol. Metab. 83:1025–1028, 1998.

    PubMed  CAS  Google Scholar 

  84. Aronica, S.M., Kraus, W.L., Katzenellenbogen, B.S. Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proc. Natl. Acad. Sci. USA 91:8517–8521, 1994.

    PubMed  CAS  Google Scholar 

  85. Rosen, J.M., Humphreys, R., Krnacik, S., Juo, P., Raught, B. The regulation of mammary gland development by hormones, growth factors, and oncogenes. Prog. Clin. Biol. Res. 387:95–110, 1994.

    PubMed  CAS  Google Scholar 

  86. Murphy, L.C., Dotzlaw, H., Leygue, E., Coutts, A., Watson, P. The regulation of mammary gland development by hormones, growth factors, and oncogenes. J. Steroid Biochem. Mol. Biol. 65:175–180, 1998.

    PubMed  CAS  Google Scholar 

  87. Ball, P., Knuppen, R. Catecholestrogens (2-and 4-hydroxy-oestrogens). Chemistry, biosynthesis, metabolism, occurrence and physiological significance. Acta Endocrinol. (Copenh.) 232(suppl): 1:127, 1980.

    Google Scholar 

  88. Zhu, B.T., Bui, Q.D., Weisz, J., Liehr, J.G. Conversion of estrone to 2-and 4-hydroxyestrone by hamster kidney and liver microsomes: Implications for the mechanism of estrogen-induced carcinogenesis. Endocrinology 135:1772–1779, 1994.

    PubMed  CAS  Google Scholar 

  89. Ashburn, S.P., Han, X., Liehr, J.G. Microsomal hydroxylation of 2-and 4-fluoroestradiol to catechol metabolites and their conversion to methyl ethers: Catechol estrogens as possible mediators of hormonal carcinogenesis. Mol. Pharmacol. 43:534–541, 1993.

    PubMed  CAS  Google Scholar 

  90. Knuppen, R., Ball, P., Emons, G. Importance of A-ring substitution of estrogens for the physiology and pharmacology of reproduction. J. Steroid Biochem. 24:193–198, 1986.

    PubMed  CAS  Google Scholar 

  91. Osborne, M.P., Bradlow, H.L, Wong, G.Y.C., Telang, N.T. Upregulation of estradiol C16 alpha-hydroxylation in human breast tissue: a potential biomarker of breast cancer risk. J. Natl. Cancer Inst. 85:1917–1920, 1993.

    PubMed  CAS  Google Scholar 

  92. Sipe, H.J. Jr., Jordan, S.J., Hanna, P.M., Mason, R.P. The metabolism of 17 beta-estradiol by lactoperoxidase: a possible source of oxidative stress in breast cancer. Carcinogenesis 15:2637–2643, 1994.

    PubMed  CAS  Google Scholar 

  93. Malins, D.C., Holmes, E.H., Polissar, N.L., Gunselman, S.J. The etiology of breast cancer. Characteristic alteration in hydroxyl radical-induced DNA base lesions during oncogenesis with potential for evaluating incidence risk. Cancer 71,3036–3043, 1993.

    PubMed  CAS  Google Scholar 

  94. Cavalieri, E.L., Stack, D.E., Devanesan, P.D., Todorovic, R., Dwivedy, I., Higginbotham, S., Johansson, S.L., Patil, K.D., Gross, M.L., Gooden, J.K., Ramanathan, R., Cerny, R.L., and Rogan, E.G. Molecular origin of cancer: Catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc. Natl. Acad. Sci. USA 99:10937–10942, 1997.

    Google Scholar 

  95. Li, J.J. and Li, S.A. Estrogen carcinogenesis in Syrian hamster tissue: role of metabolism. Fed. Proc. 46:1858–1863, 1987.

    PubMed  CAS  Google Scholar 

  96. Furth, J. Hormones as etiological agents in neoplasia. In: Becker FF (ed) Cancer. A Comprehensive Treatise. 1. Etiology: Chemical and Physical Carcinogenesis. Plenum Press, New York, Chapt. 4, 1982, pp 89–134.

    Google Scholar 

  97. Li, J.J. and Li, S.A. Estrogen carcinogenesis in hamster tissues: A critical review. Endocr. Rev. 11, 524–531, 1990.

    PubMed  CAS  Google Scholar 

  98. Li, J.J. Estrogen carcinogenesis in hamster tissues: Update. Endocr. Rev. 1:94–95, 1993.

    Google Scholar 

  99. Liehr, J.G. Is estradiol a genotoxic mutagenic carcinogen? Endocr. Rev. 21:40–54, 2000.

    PubMed  CAS  Google Scholar 

  100. Cavalieri, E., Frenkel, K., Liehr, J.G., Rogan, E., Roy, D. Estrogens as endogenous genotoxic agents-DNA adducts and mutations. J. Natl. Cancer Inst. Monograph 27:75–93, 2000.

    CAS  Google Scholar 

  101. Liehr, J.G. Genotoxicity of estrogens: A role in cancer development? Human reproduction Update 7:1–9, 2001.

    Google Scholar 

  102. Rajah, T.T. and Pento, J.T. The mutagenic potential of antiestrogens at the HPRT locus in V79 cells. Res. Comm. Molecul. Pathol. & Pharmacol. 89:85–92, 1995.

    CAS  Google Scholar 

  103. Kong, L-Y., Szaniszlo, P., Albrecht, T. and Liehr, J.G. Frequency and molecular analysis of HPRT mutations induced by estradiol in Chinese hamster V79 cells. Intl. J. Oncol. 17, 1141–1149, 2000.

    CAS  Google Scholar 

  104. Tsutsui, T., Tamura, Y., Yagi, E. Involvement of genotoxic effects in the initiation of estrogen-induced cellular transformation: studies using Syrian hamster embryo cells treated with 17β-estradiol and eight of its metabolites. Int. J. Cancer 86:8–14, 2000.

    PubMed  CAS  Google Scholar 

  105. Russo, J., Hu, Y.F., Tahin, Q., Mihaila, D., Slater, C., Lareef, M.H. and Russo, I.H. Carcinogenicity of Estrogens in Human breast epithelial cells. Acta Pathologica, Micro-biologica Immunologica Scandinavica (APMIS) 109:39–52, 2001.

    CAS  Google Scholar 

  106. Thibodeau, P.A., Bissonnette, N., Bedard, S.K., et al. Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells. Carcinogenesis 19:1545–1552, 1998.

    PubMed  CAS  Google Scholar 

  107. Hodgson, A.V., Ayala-Torres, S. and Thompson, E.B. and Liehr, J.G. Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis. Carcinogenesis, 19:2169–2172, 1888.

    Google Scholar 

  108. Loeb, L.A. A Mutator Phenotype in Cancer. Perspec. In Can. Res. 61:3230–3239, 2001.

    CAS  Google Scholar 

  109. Boyd, J., Takahashi, H., Waggoner, S.E., Jones, L.A., Hajek, R.A., Wharton, J.T., Liu, F.S., Fujino, T., McLachlan, J.A. Molecular genetics analysis of clear cell adenocarcinomas of the vagina associated and unassociated with diethylstilbestrol exposure in utero. Cancer 77:507–513, 1996.

    PubMed  CAS  Google Scholar 

  110. Richard, S.M., Bailliet, G., Paez, G.L., Bianchi, M.S., Peltomaki, P., Bianchi, N.O. Nuclear and mitochondrial genome instability in human breast cancer. Cancer. Res. 60:4231–4237, 2000.

    PubMed  CAS  Google Scholar 

  111. Forgacs, E., Wren, J.D., Kamibayashi, C., Kondo, M., Xu, X.L., Markowitz, S., Tomlinson, G.E., Muller, C.Y., Gazdar, A.F., Garner, H.R., Minna, J.D. Searching for microsatellite mutations in coding regions in lung, breast, ovarian and colorectal cancers. Oncogene 20,1005–1009, 2001.

    PubMed  CAS  Google Scholar 

  112. Piao, Z., Lee, K.S., Kim, H., Perucho, M., Malkhosyan, S. Identification of novel deletion regions of chromosome arms 2q and 6p in breast carcinomas by amplotype analysis. Genes, Chromosomes & Cancer 30:113–122, 2001.

    CAS  Google Scholar 

  113. Caldes, T., Perez-Segura, P., Tosar, A., de La Hoya, M., Diaz-Rubio, E. Microsatellite instability correlates with negative expression of estrogen and progesterone receptors in sporadic breast cancer. Teratogenesis, Carcinogenesis, & Mutagenesis. 20: 283–291, 2000.

    CAS  Google Scholar 

  114. Miyazaki, M., Tamaki, Y, Sakita, I., Fujiwara, Y, Kodta, M., Masuda, N., Ooka, M., et al. Detection of microsatellite alterations in nipple discharge accompanied by breast cancer. Breast Cancer Research & Treatment 60:35–41, 2000.

    CAS  Google Scholar 

  115. Ando, Y, Iwase, H., Ichihara, S., Toyoshima, S., Nakamura, T., Yamashita, H., et al. Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast. Cancer Letters. 156:207–214, 2000.

    PubMed  CAS  Google Scholar 

  116. Tokunaga, E., Oki, E., Oda, S., Kataoka, A., Kitamura, K., Ohno, S., Maehara, Y, Sugimachi, K. Frequency of microsatellite instability in breast cancer determined by high-resolution fluorescent microsatellite analysis. Oncology 59:44–49, 2000.

    PubMed  CAS  Google Scholar 

  117. Shaw, J.A., Smith, B.M., Walsh, T., Johnson, S., Promrose, L., Slade, M.J., Walker, R.A., Coombes, R.C. Microsatellite alterations plasma DNA of primary breast cancer patients. Clinical Cancer Research. 6:1119–1124, 2000.

    PubMed  CAS  Google Scholar 

  118. Cavalieri, E.L., and Rogan, E.G. The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. Pharmacol. Ther. 55:183–99, 1992.

    PubMed  CAS  Google Scholar 

  119. Cavalieri, E.L., and Rogan, E.G. Mechanisms of tumor initiation by polycyclic aromatic hydrocarbons in mammals. In: The Handbook of Environmental Chemistry: PAHs and Related Compounds (Neilson, A.H., Ed.) 1998, Vol. 3 J, pp 81–117, Springer, Heidelberg, Germany.

    Google Scholar 

  120. Chakravarti, D., Pelling, J.C., Cavalieri, E.L. and Rogan, E.G. Relating aromatic hydrocarbon-induced DNA adducts and c-Harvey-ras mutations in mouse skin papillomas: The role of apurinic sites. Proc. Natl. Acad. Sci. USA 92:10422–10426, 1995.

    PubMed  CAS  Google Scholar 

  121. Liehr, J.G., Fang, WE, Sirbasku, D.A. and Ari-Ulubelen, A. Carcinogenicity of catecholestrogens in Syrian hamsters. J. Steroid Biochem. 24:353–356, 1986.

    PubMed  CAS  Google Scholar 

  122. Li, K.M., Devanesan, P.D., Rogan, E.G., and Cavalieri, E.L. Formation of the depurinating 4-hydroxyestradiol (4-OHE2)-1-N7Gua and 4-OHE2-l-N3Ade adducts by reaction of E2-3,4-quinone with DNA. Proc. Am. Assoc. Cancer Res. 39:636, 1998.

    Google Scholar 

  123. Chakravarti, D., Mailander, P., Franzen, J., Higginbotham, S., Cavalieri, E. and Rogan, E. Detection of dibenzo[a,l]pyrene-induced H-ras codon 61 mutant genes in preneoplastic SENCAR mouse skin using a new PCR-RFLP method. Oncogene, 16:3203–3210, 1998.

    PubMed  CAS  Google Scholar 

  124. Miller, W.R. and O’Neill, J. The importance of local synthesis of estrogen within the breast. Steroids 50:537–548, 1987.

    PubMed  CAS  Google Scholar 

  125. Simpson, E.R., Mahendroo, M.S., Means, G.D., Kilgore, M.W., Hinsheiwood, M.M., Graham-Lorence, S., et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocrine Rev. 15:342–355, 1994.

    CAS  Google Scholar 

  126. Yue, W, Wang, J.P., Hamilton, C.J., Demers, L.M., and Santen, R.J. In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Research 58:927–932, 1998.

    PubMed  CAS  Google Scholar 

  127. Yue, W., Santen, R.J., Wang, J.P., Hamilton, C.J., and Demers, L.M., Aromatase within the breast. Endocrine-Related Cancer 6:157–164, 1999.

    PubMed  CAS  Google Scholar 

  128. Jefcoate, C.R., Liehr, J.G., Santen, R.J., Sutter, T.R., Yager, J.D., Yue, W., Santner, S.J., Tekmal, R., Demers, L., Pauley, R., Naftolin, F., Mor, G., and Berstein, L. Tissue-specific synthesis and oxidative metabolism of estrogens. In: JNCI Monograph 27: Estrogens as Endogenous Carcinogens in the Breast and Prostate (E. Cavalieri and E. Rogan, Eds.), Oxford Press, 2000,95–112.

    Google Scholar 

  129. Reed, M.J., and Purohit, A. Breast cancer and the role of cytokines in regulating estrogen synthesis: An emerging hypothesis. Endocrine Review 18:701–715, 1997.

    CAS  Google Scholar 

  130. Spink, D.C., Hayes, C.L., Young, N.R., Christou, M., Sutter, T.R., Jefcoate, C.R., et al. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: Evidence for induction of a novel 17β-estradiol 4-hydroxylase. J. Steroid Biochem. Mol. Biol. 51:251–258, 1994.

    PubMed  CAS  Google Scholar 

  131. Hayes, C.L, Spink, D.C., Spink, B.C., Cao, J.Q., Walker, N.J., and Sutter, T.R. 17β-Estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc. Natl. Acad. Sci. USA 93:9776–9781, 1996.

    PubMed  CAS  Google Scholar 

  132. Spink, D.C., Spink, B.C., Cao, J.Q., DePasquale, J.A., Pentecost, B.T., Fasco, M.J., et al. Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells. Carcinogenesis 19:291–298, 1998.

    PubMed  CAS  Google Scholar 

  133. Badawi, A.R, Devanesan, P.D., Edney, J.A., West, W.W., Higginbotham, S., Rogan, E.G., and Cavalieri, E.L. Estrogen metabolites and conjugates: Biomarkers of susceptibility to human breast cancer. Proc. Amer. Assoc. Cancer Res. 42, 664, 2001.

    Google Scholar 

  134. Visscher, D.W, Micale, M.A., Crissman, J.D. Pathological and biological relevance of cytophotometric DNA content to breast carcinoma genetic progression. J. Cell. Biochem. Suppl. 17:114–122, 1993

    Google Scholar 

  135. Berado, M.D., O’Connell, P., Allred, D.C. Biological characteristics of premalignant and preinvasive breast disease. Pasqualine, J. R. Katzenellenbogen, B.S. eds. Hormone-Dependent Cancer 1996,1–23 Marcel Dekker, Inc. New York.

    Google Scholar 

  136. Oshimura, M., Barrett, J.C. Chemically-induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer. Environ. Mutagen. 8:129–159, 1986.

    PubMed  CAS  Google Scholar 

  137. Aardema, M.J., Crosby, L.L., Gibson, D.P., Kerckaert, G.A., LeBoeuf, R.A. Aneuploidy and consistent structural chromosome changes associated with transformation of Syrian hamster embryo cells. Cancer Genet. Cytogenet. 96:140–150, 1997.

    PubMed  CAS  Google Scholar 

  138. Aldaz, C.M., Chen, T., Sohin, A., Cunningham, J., Bondy, M. Comparative allelotypes of in situ and invasive human breast cancer: high frequency of micro-satellite instability in lobular breast carcinomas. Cancer Res. 55:3976–3981, 1995.

    PubMed  CAS  Google Scholar 

  139. Pihan, G.A., Doxsey, S.J. The mitotic machinery as a source of genetic instability in cancer. Semin. Cancer Biol. 9:289–302, 1999.

    PubMed  CAS  Google Scholar 

  140. Mitelman, F., Levan, G. Clustering of aberrations on specific chromosomes in human neoplasms. A survey of 1871 cases. Hereditas 95:79–139, 1981.

    CAS  Google Scholar 

  141. Goepfert, T.M., McCarthy, M., Kittrell, F.S., Stephens, C., Ullrich, R.L., Brinkley B.R., and Medina, D. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells. The FASEB Journal 14:221–2229, 2000.

    Google Scholar 

  142. Greendale, G.A., Reboussin, B.A., Sie, A., Singh, R., Olsen, L.K., Gateswood, O., Bassett, L.W, Wasilauskas, C., Bush, T., Barrett-Connor, E. Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Ann Int. Med. 130:262–269, 1999.

    PubMed  CAS  Google Scholar 

  143. Schairer, C., Lubin, J., Troisi, R., Sturgeon, S., Brinton, L., Hoover, R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. J. Am. Med. Assoc. 283:485–491, 2000.

    CAS  Google Scholar 

  144. Ross, R.K., Paganini-Hill, A., Wan, P.C., Pike, M.C. Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J. Natl. Cancer Inst. 92:328–332, 2000.

    PubMed  CAS  Google Scholar 

  145. Fukasawa, K., Choi, T., Kuriyama, R., Rulong, S., Vande Woude, G.F. Abnormal centrosome amplification in the absence of p53. Science 271:1744–1747, 1996

    PubMed  CAS  Google Scholar 

  146. Pihan, G.A., Purohit, A., Wallace, J., Knecht, H., Woda, B., Quesenberry, P., Doxsey, S.J. Centrosome defects and genetic instability in malignant tumors. Cancer Res. 58:3974–3985, 1998.

    PubMed  CAS  Google Scholar 

  147. Zhou, H., Kuang, J., Zhong, L, Juo, W.-L, Gray, J.W, Sahin, A., Brinkley, B.R., Sen, S. Tumour amplified kinase STK15/BRAK induces centrosome amplification, aneuploidy and transformation. Nature (London) Genetics 20:189–193, 1998.

    CAS  Google Scholar 

  148. Lingle, W.L., Salisbury, J.L. Altered centrosome structure is associated with abnormal mitoses in human breast tumors. Am. J. Pathol. 155:1941–1951, 1999.

    PubMed  CAS  Google Scholar 

  149. Trent, J.M., Wiltshire, R., Su, L., Nicolaides, N.C., Vogelstein, B., Kinzler, K.W. The gene for the APC-binding protein beta-catenin (CTNNB1) maps to chromosome 3p22, a region frequently altered in human malignancies. Cytogenet. Cell Genet. 71:343–344, 1995.

    PubMed  CAS  Google Scholar 

  150. Dietrich, C.U., Pandis, N., Teixeira, M.R, Bardi, G., Gerdes, A.M., Andersen, J.A., Heim, S. Chromosome abnormalities in benign hyper-proliferative disorders of epithelial and stromal breast tissue. Int. J. Cancer 60:49–53, 1995.

    PubMed  CAS  Google Scholar 

  151. Pennisi, E. New gene forges link between fragile site and many cancers. Science 272:649, 1996.

    PubMed  CAS  Google Scholar 

  152. Cuthbert, A.R, Bond, J., Trott. D.A., Gill, S., Broni, J., Marriott, A., Khoudoli, G., Parkinson, E.K., Cooper, C.S., New-bold, R.F. Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells. J. Natl. Cancer Inst. 91:37–45, 1999.

    PubMed  CAS  Google Scholar 

  153. Negrini, M., Sabbioni, S., Haldar, S., Possati, L., Castagnoli, A., Corallini, A., Barbanti-Brodano, G., Croce, C.M. Tumor and growth suppression of breast cancer cells by chromosome 17-associated functions. Cancer Res. 54:1818–1824, 1994.

    PubMed  CAS  Google Scholar 

  154. Borresen, A.L., Andersen, T.I., Garber, J., Barbier-Piraux, N., Thorlacius, S., Eyfjord, J, Ottestad L, Smith-Sorensen B, Hovig E, Malkin D. Screening for germ line TP53 mutations in breast cancer patients. Cancer Res. 52:3234–3236, 1992.

    PubMed  CAS  Google Scholar 

  155. Puech, A., Henry, I., Jeanpierre, C., Junien, C. A highly polymorphic probe on 11p15.5: L22.5.2 (D11S774). Nucleic Acids Research 19:5095–5099, 1991.

    PubMed  CAS  Google Scholar 

  156. Hannigan, G.E., Bayani, J., Weksberg, R., Beatty, B., Pandita, A., Dedhar, S., Squire, J. Mapping of the gene encoding the integrin-linked kinase, ILK, to human chromosome 11pl5.5-pl5.4. Genomics 42:177–179, 1997.

    PubMed  CAS  Google Scholar 

  157. Wang, H., Shao, N., Ding, Q.M., Cui, J., Reddy, E.S., Rao, V.N. BRCA1 proteins arc transported to the nucleus in the absence of serum and splice variants BRCAla, BRCAlb are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases. Oncogene 15:143–157, 1997.

    PubMed  CAS  Google Scholar 

  158. Dong, J-T., Lamb, P.W, Rinker-Schaeffer, C.W., Vukanovic, J., Ichikawa, T., Isaacs, J.T., Barrett, J. KA/1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science 268:884–886, 1995.

    PubMed  CAS  Google Scholar 

  159. Wei, Y., Lukashev, M., Simon, D., et al. Regulation of integrin function by the urokinase receptor. Science 273:1551–1555, 1996.

    PubMed  CAS  Google Scholar 

  160. Hampton, G.M., Mannermaa, A., Winquist, R., Alavaikko, M., Blanco, G., Taskinen, P.G., Kiviniemi, H., Newsham, I., Cavenee, W.K., Evans, G.A. Losses of heterozygosity in sporadic human breast carcinoma: A common region between 11q22 and 11q23.3. Cancer Res. 54:4586–4589, 1994.

    PubMed  CAS  Google Scholar 

  161. Negrini, M., Rasio, D., Hampton, G.M., Sabbioni, S., Rattan, S., Carter, S.M., Rosenberg, A.L., Schwartz, G.E, Shiloh, Y., Cavenee, W.K., Croce, CM. Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: Identification of a new region at 11 q23.3. Cancer Res. 55:3003–3007, 1995.

    PubMed  CAS  Google Scholar 

  162. Winqvist, R., Hampton, G.M., Mannermaa, A., Blanco, G., Alavaiko, M., Kiviniemi, H., Taskinen, P.J., Evans, G.A., Wright, F.A., Newsham, I., Cavenee, W.K. Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis. Cancer Res. 55:2660–2664, 1995.

    PubMed  CAS  Google Scholar 

  163. Elson, A., Wang, Y, Daugherty, C.J., Morton, C.C., Zhou, E, Campos-Torres, J., Leder, P. Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proc. Natl. Acad. Sci. USA 93:13084–13089, 1996.

    PubMed  CAS  Google Scholar 

  164. Westphal, C.H., Schmaltz, C., Rowan, S., Elson, A., Fisher, D.E., Leder, P. Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints. Cancer Res. 57:1664–1667, 1997.

    PubMed  CAS  Google Scholar 

  165. Soule, H.D., Maloney, T.M., Wolman, S.R., Peterson, Jr. W.D., Brenz, R., McGrath, C.M., Russo, J., Pauley, R., Jones, R.E, Brooks, S.C. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 50:6075–6086, 1990.

    PubMed  CAS  Google Scholar 

  166. Tait, L., Soule, H., and Russo, J. Ultrastructural and immunocytochemical characterizations of an immortalized human breast epithelial cell line MCF-10. Cancer Res. 50:6087–6099, 1990.

    PubMed  CAS  Google Scholar 

  167. Calaf, G., Russo, J. Transformation of human breast epithelial cells by chemical carcinogens. Carcinogenesis 14:483–492, 1993.

    PubMed  CAS  Google Scholar 

  168. Russo, J., Calaf, G., Russo, I.H. A critical approach to the malignant transformation of human breast epithelial cells. CRC Critical Reviews in Oncogenesis 4:403–417, 1993.

    CAS  Google Scholar 

  169. Krege, J.H., Hodgin, J.B., Couse, J.F., et al. Generation and reproductive phenotypes of mice lacking oestrogen receptor β. Proc. Natl. Acad. Sci. U.S.A. 95:15677–15682, 1998.

    PubMed  CAS  Google Scholar 

  170. Paech, K., Webb, P., Kuiper, G.G., Nilsson, S., Gustafsson, J., Kushner, P.J., Scanlan, T.S. Differential ligand activation of estrogen receptors ERalpha and ERbeta at API sites. Science 277:1508–1510, 1997.

    PubMed  CAS  Google Scholar 

  171. Ali, LU, Lidereau, R., Callahan, R. Presence of two members of c-erbAB and c-erbA2 in smallest region of somatic homozygosity on chromosome 3p21-p25 in human breast carcinoma. J. Natl. Cancer Inst. 81:1815–1820, 1989.

    PubMed  CAS  Google Scholar 

  172. Chen, L-C., Matsumura, K., Deng, G., Kurisu, W, Ljung, B-M., Lerman, M.I., Waldman, F.M., Smith, H.S. Deletion of two separate regions on chromosome 3p in breast cancers. Cancer Res. 54:3021–3024, 1994.

    PubMed  CAS  Google Scholar 

  173. Bergthorsson, J.T., Eiriksdottir, G., Barkardottir, R.B., Egilsson, V., Arason, A., Ingvarsson, S. Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3. Human Genetics 96:437–443, 1995.

    PubMed  CAS  Google Scholar 

  174. Kerangueven, F., Noguchi, T., Wargniez, V. Multiple sites of loss of heterozygosity on chromosome arms 3p and 3q in human breast carcinomas. Oncology Reports 3:313–316, 1996.

    PubMed  CAS  Google Scholar 

  175. Pandis, N., Bardi, G., Mitelman, F., and Heim, S. Deletion of the short arm of chromosome 3 in breast tumors. Genes Chrom. Cancer 18:241–245, 1997.

    PubMed  CAS  Google Scholar 

  176. Man, S., Ellis, I., Sibbering, M., Blarney, R., and Brook, J. Highs level of allele loss at the FHIT and ATM genes in noncomedo ductal carcinoma in situ and grade I tubular invasive breast cancers. Cancer Res. 56:5484–5489, 1996.

    PubMed  CAS  Google Scholar 

  177. Sanchez, Y, el-Naggar, A., Pathak, S., and Killary, A.M. A tumor suppressor locus within 3pl4-pl2 mediates rapid cell death of renal cell carcinoma in vivo. Proc. Natl. Acad. Sci. USA 91:3383–3387, 1994.

    PubMed  CAS  Google Scholar 

  178. Killary, A., Wolf, M., Giambernardi, T., and Naylor, S. Definition of a tumor suppressor locus within human chromosome 3p21-p22. Proc. Natl. Acad. Sci. USA 89:10877–10881, 1992.

    PubMed  CAS  Google Scholar 

  179. Hibi, Y., Yamakawa, I.C., Ueda, R., Horio, Y. Aberrant upregulation of a novel integrin a subunit gene at 3p2 1.3 in small cell lung cancer. Oncogene 9:611–619, 1994.

    PubMed  CAS  Google Scholar 

  180. Jackers, P., Minoletti, F., Belotti, D., Clausse, N., Sozzi, G., Sobel, M.E., Castronovo, V. Isolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LRP/p40 at chromosome 3p21.3. Oncogene 13:495–503, 1996.

    PubMed  CAS  Google Scholar 

  181. Wewer, U.M., Taraboletti, G., Sobel, M.E., Albrechtsen. R., Liotta, L.A. Role of laminin receptor in tumor cell migration. Cancer Res. 47:5691–5698, 1987.

    PubMed  CAS  Google Scholar 

  182. Martignone, S., Menard, S., Bufalino, R., et al. Prognostic significance of the 67-kilodalton laminin receptor expression in human breast carcinomas. J. Natl. Cancer Inst. 85: 398–402, 1993.

    PubMed  CAS  Google Scholar 

  183. Maemura, M., and Dickson, R.B. Are cellular adhesion molecules involved in metastasis of breast cancer. Breast Cancer Res. Treat. 32:239–260, 1994.

    PubMed  CAS  Google Scholar 

  184. Ben Cheickh, M., Rouanet, P., Louason, G., Jeanteur, P., and Theillet, C. An attempt to define sets of cooperating genetic alterations in human breast cancer. Int. J. Cancer 51:542–547, 1992.

    Google Scholar 

  185. Negrini, M., Monaco, C., Vorechovsky, I., Ohta, M., Druck, T., Baffa, R., Huebner, K., Croce, C.M. The FHIT gene at 3pl4.2 is abnormal in breast carcinomas. Cancer Res. 56:3173–3179, 1996.

    PubMed  CAS  Google Scholar 

  186. Theillet, C., Lidereau, R., Escot, C., Hutzell, P., Brunet, M., Gest, J., Schlom, J., Callahan, R. Loss of a c-H-ras-I allele and aggressive human primary breast carcinomas. Cancer Res. 46:4776–4781, 1986.

    PubMed  CAS  Google Scholar 

  187. Mackay, J., Elder, P., Porteous, D.I., et al. Partial deletion of chromosome 11p in breast cancer correlates with size of primary turnout and estrogen receptor level. Br. J. Cancer 58:710–714, 1988.

    PubMed  CAS  Google Scholar 

  188. Takita, K-I., Sato, T., Miyagi, M., Watatani, M., Akiyama, F., Sakamoto, G., Kasumi, F., Abe, R., Nakamura, Y. Correlation of loss of alleles on the short arms of chromosomes 11 and 17 with metastasis of primary breast cancer to lymph nodes. Cancer Res. 52:3914–3917, 1992.

    PubMed  CAS  Google Scholar 

  189. Winqvist, R., Mannermaa, A., Alavaikko, M., Blanco, G., Taskinen, P.J., Kiviniemi, H., Newsham, I., Cavenee, W. Refinement of regional loss of heterozygosity for chromosome 11pl5.5 in human breast tumors. Cancer Res. 53:4486–4488, 1993.

    PubMed  CAS  Google Scholar 

  190. Gudmundsson, J., Barkardottir, R.B., Eiriksdottir, G., Baldursson, T., Arason, A., Egilsson, V., Ingvarsson, S. Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations. Br. J. Cancer 72:696–701, 1995.

    PubMed  CAS  Google Scholar 

  191. Deng, G., Chen, L.C., Schott, D.R., Thor, A., Bhargava, V., Ljung, B.M., Chew, K., Smith, H.S. Loss of heterozygosity and p53 gene mutations in breast cancer. Cancer Res. 54:499–505, 1994.

    PubMed  CAS  Google Scholar 

  192. Negrini, M., Sabbioni, S., Ohta, M., Veronese, M.L., Rattan, S., Junien, C., Croce, C.M. Seven-megabase yeast artificial chromosome contig at region 11pl5:Identification of a yeast artificial chromosome spanning the breakpoint of a chromosomal translocation found in a case of Beckwith-Wiedmann syndrome. Cancer Res. 55:2904–2909, 1995.

    PubMed  CAS  Google Scholar 

  193. Carter, S., Negrini, M., Baffa, R., Gillum, D.R., Rosenberg, A.L., Schwartz, G.F., Croce, C.M. Loss of heterozygosity at 11 q22-q23 in breast cancer. Cancer Res. 54:6270–6274, 1994.

    PubMed  CAS  Google Scholar 

  194. Swift, M., Morrel, D., Massey, R., Chase, C. Incidence of cancer in 161 families affected by ataxia-telangiectasia. New Eng. J. Med. 325:1831–1836, 1991.

    PubMed  CAS  Google Scholar 

  195. Byrd, P.J., Stankovic, T., McConville, C.M., Smith, A.D., Cooper, PR., Taylor, A.M. Identification and analysis of expression of human VACM-1, a cullin gene family member located on chromosome 11 q22-23. Genome Res. 7:71–75, 1997.

    PubMed  CAS  Google Scholar 

  196. Tomlinson, I.P, Nicolai, H., Solomon, E., Bodmer, W.F. The frequency and mechanism of loss of heterozygosity on chromosome 1lq in breast cancer. Journal of Pathology 180:38–43, 1996.

    PubMed  CAS  Google Scholar 

  197. Tomlinson, I.P., Beck, N.E., Bodmer, W.F. Allele loss on chromosome 1lq and microsatellite instability in malignant melanoma. European Journal of Cancer 32A:1797–802, 1996.

    PubMed  CAS  Google Scholar 

  198. Connolly, K.C, Gabra, H., Millwater, C.J., Taylor, K.J., Rabiasz, G.J., Watson, J.E., Smyth, J.F., Wvllie, A.H., Jodrell, D.I. Identification of a region of frequent loss of heterozygosity at 11 q24 in colorectal cancer. Cancer Res. 59:2806–2809, 1999.

    PubMed  CAS  Google Scholar 

  199. Launonen, V, Stenback, F., Puistola, U., Bloiu, R., Huusko, P., Kytola, S., Kauppila, A., Winqvist, R. Chromosome 11q22.3-q25 LOH in ovarian cancer: association with a more aggressive disease course and involved subregions. Gynecol. Oncol. 71:299–304, 1998.

    PubMed  CAS  Google Scholar 

  200. Dahiva, R., McCarville, J., Lee, C., Hu, W, Kaur, G., Carroll, P., Deng, G. Deletion of chromosome 1 lpl5, pl2, q22, q23-24 loci in human prostate cancer. International Journal of Cancer 72:283–288, 1997.

    Google Scholar 

  201. Yen, T.J., Li, G., Schaar, B., Szilak, I., and Cleveland, D.W. CENP-E is a putative kinetochore motor that accumulates just prior to mitosis. Nature 359:536–539, 1992.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Breast Cancer Research Laboratory, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Jose Russo MD, FACP & Irma H. Russo MD, FACP

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  1. Jose Russo MD, FACP
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  2. Irma H. Russo MD, FACP
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© 2004 Springer-Verlag Berlin Heidelberg

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Russo, J., Russo, I.H. (2004). The Role of Estrogen in Breast Cancer. In: Molecular Basis of Breast Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18736-0_4

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  • DOI: https://doi.org/10.1007/978-3-642-18736-0_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62270-0

  • Online ISBN: 978-3-642-18736-0

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