Conclusions
Thyroid tumors are common neoplasms that exhibit a wide range of biologic behavior. Numerous factors have been shown to govern thyrocyte proliferation. In particular, hormones and growth factors likely play a role as promoters of tumor cell growth in genetically transformed cells. In some instances enhanced growth factors and their receptors may serve as survival signals for neoplastic cells. In other instances, however, abnormal forms of growth factor receptors (such as members of the EGF-R/HER2/neu) may also be important in the early stages of cell transformation and chromosomal instability consistent with the clonal composition of thyroid neoplasms. More detailed structure/function studies of growth factor/receptor functional interactions in morphologically characterized thyroid nodules are required. It is anticipated that these studies will identify signaling patterns that will provide the basis for the development of more specific and effective pharmacotherapeutic agents.
This work was supported in part by grants from the Canadian Institutes of Health Research (MT-14404).
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
Keywords
- Papillary Thyroid Carcinoma
- Papillary Carcinoma
- Fibroblast Growth Factor Receptor
- Human Thyroid
- Pituitary Tumor Transforming Gene
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Rizzino A. Growth Factors. In: Kovacs K, Asa SL, editors. Functional Endocrine Pathology. Boston: Blackwell Scientific Publications Inc., 1991: 979–989.
Ezzat S. The role of hormones, growth factors and their receptors in pituitary tumorigenesis. Brain Pathol 2001; 11(3):356–370.
Asa SL, Ezzat S. The pathogenesis of pituitary tumours. Nat Rev Cancer 2002; 2(11):836–849.
van der Laan BFAM, Freeman JL, Asa SL. Expression of growth factors and growth factor receptors in normal and tumorous human thyroid tissues. Thyroid 1995; 5:67–73.
Minuto F, Barreca A, del Monte P, Cariola G, Torre GC, Giordano G. Immunoreactive insulin-like growth factor I (IGF-I) and IGF-I-binding protein content in human thyroid tissue. J Clin Endocrinol Metab 1989; 68:621–626.
Okimura Y, Kitajima N, Uchiyama T et al. Insulin-like growth factor I (IGF-I) production and the presence of IGF-I receptors in rat medullary thyroid carcinoma cell line 6-23 (clone 6). Biochem Biophys Res Commun 1989; 161:589–595.
Di Carlo A, Pisano G, Parmeggiani U, Beguinot L, Macchia V. Epidermal growth factor receptor and thyrotropin response in human thyroid tissues. J Endocrinol Invest 1990; 13:293–299.
Duh Q-Y, Gum ET, Gerend PL, Raper SE, Clark OH. Epidermal growth factor receptors in normal and neoplastic thyroid tissue. Surgery 1993; 98:1000–1007.
Grubeck-Loebenstein B, Buchan G, Sadeghi R et al. Transforming growth factor beta regulates thyroid growth. role in the pathogenesis of nontoxic goiter. J Clin Invest 1989; 83:764–770.
Aasland R, Akslen LA, Varhaug JE, Lillehaug JR. Co-expression of the genes encoding transforming growth factor-α and its receptor in papillary carcinomas of the thyroid. Int J Cancer 1990; 46:382–387.
Driman DK, Kobrin MS, Kudlow JE, Asa SL. Transforming growth factor-α in normal and neoplastic human endocrine tissues. Hum Pathol 1992; 23:1360–1365.
Heldin N-E, Gustavsson B, Claesson-Welsh L et al. Aberrant expression of receptors for platelet-derived growth factor in an anaplastic thyroid carcinoma cell line. Proc Natl Acad Sci USA 1993; 85:9302–9306.
Matsuo K, Tang S-H, Sharifi B, Rubin SA, Schreck R, Fagin JA. Growth factor production by human thyroid carcinoma cells: Abundant expression of a platelet-derived growth factor-β-like protein by a human papillary carcinoma cell line. J Clin Endocrinol Metab 1993; 77:996–1004.
Logan A, Gonzalez AM, Buscaglia ML, Black EG, Sheppard MC. Basic fibroblast growth factor is an autocrine factor for rat thyroid follicular cells. Ann NY Acad Sci 1991; 638:453–455.
Beerli RR, Hynes NE. Epidermal growth factor-related peptides activate distinct subsets of ErbB receptors and differ in their biological activities. J Biol Chem 1996; 271:6071–6076.
Ezzat S, Walpola IA, Ramyar L, Smyth HS, Asa SL. Membrane-anchored expression of transforming growth factor-α in human pituitary adenoma cells. J Clin Endocrinol Metab 1995; 80:534–539.
Fisher DA, Lakshmanan J. Metabolism and effects of epidermal growth factor and related growth factors in mammals. Endocr Rev 1990; 11:418–442.
Bates SE, Davidson NE, Valverius EM et al. Expression of transforming growth factor α and its messenger ribonucleic acid in human breast cancer: Its regulation by estrogen and its possible functional significance. Mol Endocrinol 1988; 2:543–555.
Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS, Kidwell WR. Expression of transforming growth factor α (TGFα) in differentiated rat mammary tumors: estrogen induction of TGFα production. Mol Endocrinol 1987; 1:683–692.
Nelson KG, Takahashi T, Lee DC et al. Transforming growth factor-α is a potential medicator of estrogen action in the mouse uterus. Endocrinology 1992; 131:1657–1664.
Son HY, Nishikawa A, Kanki K et al. Synergistic interaction between excess caffeine and deficient iodine on the promotion of thyroid carcinogenesis in rats pretreated with N-bis (2-hydroxypropyl) nitrosamine. Cancer Sci 2003; 94(4):334–337.
Mäkinen T, Pekonen F, Franssila K, Lamberg B-A. Receptors for epidermal growth factor and thyrotropin in thyroid carcinoma. Acta Endocrinol (Copen) 1988; 117:45–50.
Marti U, Ruchti C, Kampf J et al. Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues. Thyroid 2001; 11(2): 137–145.
Carlomagno F, Vitagliano D, Guida T et al. ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 2002; 62(24):7284–7290.
Qian X, LeVea CM, Freeman JK, Dougall WC, Greene MI. Heterodimerization of epidermal growth factor receptor and wild-type or kinase-deficient Neu: A mechanism of interreceptor kinase activation and transphosphorylation. Proc Natl Acad Sci USA 1994; 91;1500–1504.
Dougall WC, Quan X, Peterson NC, Miller MJ, Samanta A, Greene MI. The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies. Oncogene 1994; 9:2109–2123.
Goldman R, Levy RB, Peles E, Yarden Y. Heterodimerization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells; A mechanism for receptor transregulation. Biochem J 1990; 29:11024–11028.
Sugg SL, Ezzat S, Zheng L, Freeman JL, Rosen IB, Asa SL. Oncogene profile of papillary thyroid carcinoma. Surgery 1999; 125:46–52.
Grande M, Franzen A, Karlsson JO, Ericson LE, Heldin NE, Nilsson M. Transforming growth factorbeta and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes. J Cell Sci 2002; 115(Pt 22):4227–4236.
Banerjee SK, Sarkar DK, Weston AP, De A, Campbell DR. Over expression of vascular endothelial growth factor and its receptor during the development of estrogen-induced rat pituitary tumors may mediate estrogen-initiated tumor angiogenesis. Carcinogenesis 1997; 18(6): 1155–1161.
Banerjee SK, Zoubine MN, Tran TM, Weston AP, Campbell DR. Overexpression of vascular endothelial growth factor164 and its co-receptor neuropilin-1 in estrogen-induced rat pituitary tumors and GH3 rat pituitary tumor cells. Int J Oncol 2000; 16(2):253–260.
Mason IJ. The ins and outs of fibroblast growth factors. Cell 1994; 78:547–552.
Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev 1987; 8:95–114.
Boelaert K, McCabe CJ, Tannahill LA et al. Pituitary tumor transforming gene and fibroblast growth factor-2 expression: potential prognostic indicators in differentiated thyroid cancer. J Clin Endocrinol Metab 2003; 88(5):2341–2347.
Komorowski J, Pasieka Z, Jankiewicz-Wika J, Stepien H. Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer. Thyroid 2002; 12(8):655–662.
Givol D, Yayon A. Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. FASEB J 1992; 6(15):3362–3369.
Yan G, Wang F, Fukabori Y, Sussman D, Hou J, McKeehan WL. Expression and transformation of a variant of the heparin-binding fibroblast growth factor receptor (flg) gene resulting from splicing of the exon at alternate 3’-acceptor site. Biochem Biophys Res Commun 1992; 183:423–430.
Peters KG, Werner S, Chen G, Williams LT. Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Develop 1992; 114:233–243.
Hanneken A, Ying W, Ling N, Baird A. Identification of soluble forms of the fibroblast growth factor receptor in blood. Proc Natl Acad Sci USA 1994; 91:9170–9174.
Werner S, Weinberg W, Liao X et al. Targeted expression of a dominant-negative FGF receptor mutant in the epidermis of transgenic mice reveals a role of FGF in keratinocyte organization and differentiation. EMBO J 1993; 12:2635–2643.
Gonzalez AM, Logan A, Ying W, Lappi DA, Berry M, Baird A. Fibroblast growth factor in the hypothalamic-pituitary axis: Differential expression of fibroblast growth factor-2 and a high affinity receptor. Endocrinology 1994; 134:2289–2297.
Eisemman A, Ahn AJ, Graziani G, Tronick SR, Ron D. Alternative splicing generates at least five different isoforms of the human bFGF receptor. Oncogene 1991; 6:1195–1202.
Becker D, Lee PLP, Rodeck U, Herlyn M. Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. Oncogene 1992; 7:2303–2313.
Yan G, Fukabori Y, McBride G, Nikolaropolous S, McKeehan WL. Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy. Mol Cell Biol 1993; 13:4513–4522.
Revest JM, Spencer-Dene B, Kerr K, De Moerlooze L, Rosewell I, Dickson C. Fibroblast growth factor receptor 2-IIIb acts upstream of Shh and Fgf4 and is required for limb bud maintenance but not for the induction of Fgf8, Fgf10, Msx1, or Bmp4. Dev Biol 2001; 231(1):47–62.
Onose H, Emioto N, Sugihara H, Shimizu K, Wakabayashi I. Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures. Eur J Endocrinol 1999; 140(2): 169–173.
Ranzi V, Meakin SO, Miranda C, Mondellini P, Pierotti MA, Greco A. The signaling adapters fibroblast growth factor receptor substrate 2 and 3 are activated by the thyroid TRK oncoproteins. Endocrinology 2003; 144(3):922–928.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Science + Business Media, Inc.
About this chapter
Cite this chapter
Ezzat, S. (2005). Growth Factors and their Receptors in the Genesis and Treatment of Thyroid Cancer. In: Farid, N.R. (eds) Molecular Basis of Thyroid Cancer. Cancer Treatment and Research, vol 122. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8107-3_6
Download citation
DOI: https://doi.org/10.1007/1-4020-8107-3_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4020-8106-4
Online ISBN: 978-1-4020-8107-1
eBook Packages: MedicineMedicine (R0)