Abstract
Genetically engineered mouse models have become fundamental tools in the basic and translational research of prostate cancer. There is a plethora of models available to dissect the genetic alterations and aberrant signaling events associated with human prostate cancer and, furthermore, to investigate new and “personalized” therapies to treat the disease. In this chapter, we discuss some of the models recently and currently used to study prostate cancer in vivo, and some considerations when selecting an appropriate model to investigate particular aspects of the disease. We describe the methods required to isolate prostate tumors and conduct basic characterization of the tumor to determine tumor load and histopathology. We also discuss important aspects to be considered when processing samples for further analysis.
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References
CRUK (2012) World cancer factsheet. CancerStats Cancer Research, UK
Abate-Shen C, Shen MM (2000) Molecular genetics of prostate cancer. Genes Dev 14(19):2410–2434
Valkenburg KC, Williams BO (2011) Mouse models of prostate cancer. Prostate Cancer 2011:895238. doi:10.1155/2011/895238
Shappell SB, Thomas GV, Roberts RL, Herbert R, Ittmann MM, Rubin MA, Humphrey PA, Sundberg JP, Rozengurt N, Barrios R, Ward JM, Cardiff RD (2004) Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee. Cancer Res 64(6):2270–2305
Di Cristofano A, De Acetis M, Koff A, Cordon-Cardo C, Pandolfi PP (2001) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat Genet 27(2):222–224. doi:10.1038/84879
Abate-Shen C, Banach-Petrosky WA, Sun X, Economides KD, Desai N, Gregg JP, Borowsky AD, Cardiff RD, Shen MM (2003) Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Cancer Res 63(14):3886–3890
Couto SS, Cao M, Duarte PC, Banach-Petrosky W, Wang S, Romanienko P, Wu H, Cardiff RD, Abate-Shen C, Cunha GR (2009) Simultaneous haploinsufficiency of Pten and Trp53 tumor suppressor genes accelerates tumorigenesis in a mouse model of prostate cancer. Differentiation 77(1):103–111. doi:10.1016/j.diff.2008.09.010
Di Cristofano A, Pesce B, Cordon-Cardo C, Pandolfi PP (1998) Pten is essential for embryonic development and tumour suppression. Nat Genet 19(4):348–355. doi:10.1038/1235
Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, Cunha GR, Donjacour AA, Matusik RJ, Rosen JM (1995) Prostate cancer in a transgenic mouse. Proc Natl Acad Sci U S A 92(8):3439–3443
Ahmad I, Sansom OJ, Leung HY (2008) Advances in mouse models of prostate cancer. Expert Rev Mol Med 10:e16. doi:10.1017/S1462399408000689
Kasper S, Sheppard PC, Yan Y, Pettigrew N, Borowsky AD, Prins GS, Dodd JG, Duckworth ML, Matusik RJ (1998) Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer. Lab Investig 78(6):i–xv
Sauer B, Henderson N (1989) Cre-stimulated recombination at loxP-containing DNA sequences placed into the mammalian genome. Nucleic Acids Res 17(1):147–161
Cleutjens KB, van der Korput HA, Ehren-van Eekelen CC, Sikes RA, Fasciana C, Chung LW, Trapman J (1997) A 6-kb promoter fragment mimics in transgenic mice the prostate-specific and androgen-regulated expression of the endogenous prostate-specific antigen gene in humans. Mol Endocrinol 11(9):1256–1265. doi:10.1210/mend.11.9.9974
Maddison LA, Nahm H, DeMayo F, Greenberg NM (2000) Prostate specific expression of Cre recombinase in transgenic mice. Genesis 26(2):154–156
Wu X, Wu J, Huang J, Powell WC, Zhang J, Matusik RJ, Sangiorgi FO, Maxson RE, Sucov HM, Roy-Burman P (2001) Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech Dev 101(1–2):61–69
Sciavolino PJ, Abrams EW, Yang L, Austenberg LP, Shen MM, Abate-Shen C (1997) Tissue-specific expression of murine Nkx3.1 in the male urogenital system. Dev Dyn 209(1):127–138. doi:10.1002/(SICI)1097-0177(199705)209:1<127::AID-AJA12>3.0.CO;2-Z
Wang X, Kruithof-de Julio M, Economides KD, Walker D, Yu HL, Halili MV, Hu YP, Price SM, Abate-Shen C, Shen MM (2009) A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461(7263):495–U461. doi:10.1038/Nature08361
Metzger D, Chambon P (2001) Site- and time-specific gene targeting in the mouse. Methods 24(1):71–80. doi:10.1006/meth.2001.1159
Greenberg NM, DeMayo FJ, Sheppard PC, Barrios R, Lebovitz R, Finegold M, Angelopoulou R, Dodd JG, Duckworth ML, Rosen JM et al (1994) The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. Mol Endocrinol 8(2):230–239. doi:10.1210/mend.8.2.8170479
Lawson DA, Witte ON (2007) Stem cells in prostate cancer initiation and progression. J Clin Invest 117(8):2044–2050. doi:10.1172/JCI32810
Birbach A (2013) Use of PB-Cre4 Mice for Mosaic Gene Deletion. Plos One 8 (1). doi:ARTN e53501, DOI 10.1371/journal.pone.0053501
Kim MJ, Bhatia-Gaur R, Banach-Petrosky WA, Desai N, Wang YZ, Hayward SW, Cunha GR, Cardiff RD, Shen MM, Abate-Shen C (2002) Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res 62(11):2999–3004
Grizzle WE (2009) Special symposium: fixation and tissue processing models. Biotech Histochem 84(5):185–193. doi:10.1080/10520290903039052
Fischer AH, Jacobson KA, Rose J, Zeller R (2008) Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008:pdb prot4986. doi:10.1101/pdb.prot4986
Scholzen T, Gerdes J (2000) The Ki-67 protein: From the known and the unknown. J Cell Physiol 182(3):311–322, 10.1002/(Sici)1097-4652(200003)182:3<311::Aid-Jcp1>3.0.Co;2-9
Patel R, Gao M, Ahmad I, Fleming J, Singh LB, Rai TS, McKie AB, Seywright M, Barnetson RJ, Edwards J, Sansom OJ, Leung HY (2013) Sprouty2, PTEN, and PP2A interact to regulate prostate cancer progression. J Clin Investig 123(3):1157–1175. doi:10.1172/Jci63672
Acknowledgements
Work in our laboratory is funded by Cancer Research UK, Medical Research Council and Prostate Cancer UK.
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Brzezinska, E.A., Nixon, C., Patel, R., Leung, H.Y. (2015). Genetically Engineered Mouse Models to Study Prostate Cancer. In: Eferl, R., Casanova, E. (eds) Mouse Models of Cancer. Methods in Molecular Biology, vol 1267. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2297-0_4
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DOI: https://doi.org/10.1007/978-1-4939-2297-0_4
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