In vitro and in vivo model systems used in prostate cancer research

Main Article Content

David Cunningham
Zongbing You


prostate cancer, cell lines, intratibial injection, mouse models, xenograft


New incidence of prostate cancer is a major public health issue in the Western world, and has been rising in other areas of the globe in recent years. In an effort to understanding the molecular pathogenesis of this disease, numerous cell models have been developed, arising mostly from patient biopsies. The introduction of the genetically engineered mouse in biomedical research has allowed the development of murine models that allow for the investigation of tumorigenic and metastatic processes. Current challenges to the field include lack of an animal model that faithfully recapitulates bone metastasis of prostate cancer.


Download data is not yet available.


Metrics Loading ...
Abstract 263 | HTML Downloads 1155 PDF Downloads 659


1. American Cancer Society. (2014) Prostate Cancer: Detailed Guide. Cited November 21, 2014. Available from 2. Lesko SM, Rosenberg L, Shapiro S. (1996) Family history and prostate cancer risk. Am J Epidemiol. 1996;144(11):1041-7.
3. Cullen J, Elsamanoudi S, Brassell SA, Chen Y, Colombo M, Srivastava A, et al. (2012) The burden of prostate cancer in Asian nations. J Carcinog. 2012;11:7.
4. Albright F, Stephenson RA, Agarwal N, Teerlink CC, Lowrance WT, Farnham JM, et al. (2014) Prostate cancer risk prediction based on complete prostate cancer family history. Prostate. 2014.
5. Ha YS, Salmasi A, Karellas M, Singer EA, Kim JH, Han M, et al. (2013) Increased incidence of pathologically nonorgan confined prostate cancer in African-American men eligible for active surveillance. Urology. 2013;81(4):831-5.
6. Sundquist K, Sundquist J, Ji J. (2014) Contribution of shared environmental factors to familial aggregation of common cancers: an adoption study in Sweden. Eur J Cancer Prev. 2014.
7. Dybkowska E, Swiderski F, Waszkiewicz-Robak B. (2014) Fish intake and risk of prostate cancer. Postepy Hig Med Dosw (Online). 2014;68(0):1199-205.
8. Beyene D, Daremipouran M, Apprey V, Williams R, Ricks-Santi L, Kassim OO, et al. (2014) Use of Tanning Potential as a Predictor for Prostate Cancer Risk in African-American Men. In Vivo. 2014;28(6):1181-7.
9. Wright JL, Neuhouser ML, Lin DW, Kwon EM, Feng Z, Ostrander EA, et al. (2011) AMACR polymorphisms, dietary intake of red meat and dairy and prostate cancer risk. Prostate. 2011;71(5):498-506.
10. Shahabi A, Corral R, Catsburg C, Joshi AD, Kim A, Lewinger JP, et al. (2014) Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study. Cancer Med. 2014.
11. Sfanos KS, De Marzo AM. (2012) Prostate cancer and inflammation: the evidence. Histopathology. 2012;60(1):199-215.
12. Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A. (2014) Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol. 2014;38(4):329-38.
13. Nakai Y, Nelson WG, De Marzo AM. (2007) The dietary charred meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine acts as both a tumor initiator and promoter in the rat ventral prostate. Cancer Res. 2007;67(3):1378-84.
14. Blanker MH, Noordzij MA. (2014) Prostate cancer screening benefit very low, even after 13 years. Ned Tijdschr Geneeskd. 2014;158(0):A8349.
15. Duffy MJ. (2014) PSA in screening for prostate cancer: more good than harm or more harm than good? Adv Clin Chem. 2014;66:1-23.
16. Thakur V, Talwar M, Singh PP. (2014) Low free to total PSA ratio is not a good discriminator of chronic prostatitis and prostate cancer: An Indian experience. Indian J Cancer. 2014;51(3):335-7.
17. Prostate Cancer Cell Line Database. BC Cancer Agency. (2001) Cited November 21, 2014. Available from
18. Sobel RE, Sadar MD. (2005) Cell lines used in prostate cancer research: a compendium of old and new lines--part 1. J Urol. 2005;173(2):342-59.
19. Sobel RE, Sadar MD. (2005) Cell lines used in prostate cancer research: a compendium of old and new lines--part 2. J Urol. 2005;173(2):360-72.
20. Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF. (1978) Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer. 1978;21(3):274-81.
21. Heinlein CA, Chang C. (2004) Androgen receptor in prostate cancer. Endocr Rev. 2004;25(2):276-308.
22. Bajgelman MC, Strauss BE. (2006) The DU145 human prostate carcinoma cell line harbors a temperature-sensitive allele of p53. Prostate. 2006;66(13):1455-62.
23. Fraser M, Zhao H, Luoto KR, Lundin C, Coackley C, Chan N, et al. (2012) PTEN deletion in prostate cancer cells does not associate with loss of RAD51 function: implications for radiotherapy and chemotherapy. Clin Cancer Res. 2012;18(4):1015-27.
24. Webber MM, Bello D, Quader S. (1997) Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications Part 2. Tumorigenic cell lines. Prostate. 1997;30(1):58-64.
25. Mickey DD, Stone KR, Wunderli H, Mickey GH, Vollmer RT, Paulson DF. (1977) Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice. Cancer Res. 1977;37(11):4049-58.
26. Bastide C, Bagnis C, Mannoni P, Hassoun J, Bladou F. (2002) A Nod Scid mouse model to study human prostate cancer. Prostate Cancer Prostatic Dis. 2002;5(4):311-5.
27. Billström A, Lecander I, Dagnaes-Hansen F, Dahllöf B, Stenram U, Hartley-Asp B. (1995) Differential expression of uPA in an aggressive (DU 145) and a nonaggressive (1013L) human prostate cancer xenograft. Prostate. 1995;26(2):94-104.
28. Hanahan D, Weinberg RA. (2011) Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-74.
29. Carruba G, Leake RE, Rinaldi F, Chalmers D, Comito L, Sorci C, et al. (1994) Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells. Steroids. 1994;59(7):412-20.
30. Pietrzkowski Z, Mulholland G, Gomella L, Jameson BA, Wernicke D, Baserga R. (1993) Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor 1. Cancer Res. 1993;53(5):1102-6.
31. Green JB. (2004) Lkb1 and GSK3-beta: kinases at the center and poles of the action. Cell Cycle. 2004;3(1):12-4.
32. Xu P, Cai F, Liu X, Guo L. (2014) LKB1 suppresses proliferation and invasion of prostate cancer through hedgehog signaling pathway. Int J Clin Exp Pathol. 2014;7(12):8480-8.
33. Yun H, Lee M, Kim SS, Ha J. (2005) Glucose deprivation increases mRNA stability of vascular endothelial growth factor through activation of AMP-activated protein kinase in DU145 prostate carcinoma. J Biol Chem. 2005;280(11):9963-72.
34. Shirahama T, Sakakura C, Sweeney EA, Ozawa M, Takemoto M, Nishiyama K, et al. (1997) Sphingosine induces apoptosis in androgen-independent human prostatic carcinoma DU-145 cells by suppression of bcl-X(L) gene expression. FEBS Lett. 1997;407(1):97-100.
35. Nutt LK, Chandra J, Pataer A, Fang B, Roth JA, Swisher SG, et al. (2002) Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis. J Biol Chem. 2002;277(23):20301-8.
36. von Haefen C, Wieder T, Gillissen B, Stärck L, Graupner V, Dörken B, et al. (2002) Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells. Oncogene. 2002;21(25):4009-19.
37. Marcelli M, Marani M, Li X, Sturgis L, Haidacher SJ, Trial JA, et al. (2000) Heterogeneous apoptotic responses of prostate cancer cell lines identify an association between sensitivity to staurosporine-induced apoptosis, expression of Bcl-2 family members, and caspase activation. Prostate. 2000;42(4):260-73.
38. Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol. 1979;17(1):16-23.
39. Keer HN, Kozlowski JM, Tsai YC, Lee C, McEwan RN, Grayhack JT. (1990) Elevated transferrin receptor content in human prostate cancer cell lines assessed in vitro and in vivo. J Urol. 1990;143(2):381-5.
40. Rossi MC, Zetter BR. (1992) Selective stimulation of prostatic carcinoma cell proliferation by transferrin. Proc Natl Acad Sci U S A. 1992;89(13):6197-201.
41. Ching KZ, Ramsey E, Pettigrew N, D'Cunha R, Jason M, Dodd JG. (1993) Expression of mRNA for epidermal growth factor, transforming growth factor-alpha and their receptor in human prostate tissue and cell lines. Mol Cell Biochem. 1993;126(2):151-8.
42. van Bokhoven A, Varella-Garcia M, Korch C, Hessels D, Miller GJ. (2001) Widely used prostate carcinoma cell lines share common origins. Prostate. 2001;47(1):36-51.
43. Barlaam B, Cosulich S, Degorce S, Fitzek M, Green S, Hancox U, et al. (2015) Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (AZD8186): a potent and selective inhibitor of PI3Kβ and PI3Kδ for the treatment of PTEN-deficient cancers. J Med Chem. 2015;58(2):943-62.
44. Tai S, Sun Y, Squires JM, Zhang H, Oh WK, Liang CZ, et al. (2011) PC3 is a cell line characteristic of prostatic small cell carcinoma. Prostate. 2011;71(15):1668-79.
45. Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, Papsidero L, et al. (1980) The LNCaP cell line--a new model for studies on human prostatic carcinoma. Prog Clin Biol Res. 1980;37:115-32.
46. Veldscholte J, Ris-Stalpers C, Kuiper GG, Jenster G, Berrevoets C, Claassen E, et al. (1990) A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun. 1990;173(2):534-40.
47. Connolly JM, Rose DP. (1990) Production of epidermal growth factor and transforming growth factor-alpha by the androgen-responsive LNCaP human prostate cancer cell line. Prostate. 1990;16(3):209-18.
48. Nakamoto T, Chang CS, Li AK, Chodak GW. (1992) Basic fibroblast growth factor in human prostate cancer cells. Cancer Res. 1992;52(3):571-7.
49. Carroll AG, Voeller HJ, Sugars L, Gelmann EP. (1993) p53 oncogene mutations in three human prostate cancer cell lines. Prostate. 1993;23(2):123-34.
50. Isaacs WB, Carter BS, Ewing CM. (1991) Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res. 1991;51(17):4716-20.
51. Carson JP, Kulik G, Weber MJ. (1999) Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B. Cancer Res. 1999;59(7):1449-53.
52. Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL, et al. (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res. 1994;54(10):2577-81.
53. Conley-LaComb MK, Saliganan A, Kandagatla P, Chen YQ, Cher ML, Chinni SR. (2013) PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling. Mol Cancer. 2013;12(1):85.
54. Klein KA, Reiter RE, Redula J, Moradi H, Zhu XL, Brothman AR, et al. (1997) Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. Nat Med. 1997;3(4):402-8.
55. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, et al. (2001) Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A. 2001;98(18):10314-9.
56. Reiter R, Sawyers C. (2001) Xenograft Models and the Molecular Biology of Human Prostate Cancer. In: Chung, LWK, Isaacs WB, Simons JW (editors). Prostate Cancer: Biology, Genetics, and the New Therapeutics. New York City: Humana Press. pp 163-174.
57. Craft N, Chhor C, Tran C, Belldegrun A, DeKernion J, Witte ON, et al. (1999) Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res. 1999;59(19):5030-6.
58. Silvers CR, Williams K, Salamone L, Huang J, Jordan CT, Zhou H, et al. (2010) A novel in vitro assay of tumor-initiating cells in xenograft prostate tumors. Prostate. 2010;70(13):1379-87.
59. Rubin MA, Putzi M, Mucci N, Smith DC, Wojno K, Korenchuk S, et al. (2000) Rapid ("warm") autopsy study for procurement of metastatic prostate cancer. Clin Cancer Res. 2000;6(3):1038-45.
60. Korenchuk S, Lehr JE, MClean L, Lee YG, Whitney S, Vessella R, et al. (2001) VCaP, a cell-based model system of human prostate cancer. In Vivo. 2001;15(2):163-8.
61. Mertz KD, Setlur SR, Dhanasekaran SM, Demichelis F, Perner S, Tomlins S, et al. (2007) Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line: a new perspective for an old model. Neoplasia. 2007;9(3):200-6.
62. Sramkoski RM, Pretlow TG, Giaconia JM, Pretlow TP, Schwartz S, Sy MS, et al. (1999) A new human prostate carcinoma cell line, 22Rv1. In Vitro Cell Dev Biol Anim. 1999;35(7):403-9.
63. Chlenski A, Nakashiro K, Ketels KV, Korovaitseva GI, Oyasu R. (2001) Androgen receptor expression in androgen-independent prostate cancer cell lines. Prostate. 2001;47(1):66-75.
64. Tepper CG, Boucher DL, Ryan PE, Ma AH, Xia L, Lee LF, et al. (2002) Characterization of a novel androgen receptor mutation in a relapsed CWR22 prostate cancer xenograft and cell line. Cancer Res. 2002;62(22):6606-14.
65. Tan J, Sharief Y, Hamil KG, Gregory CW, Zang DY, Sar M, et al. (1997) Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells. Mol Endocrinol. 1997;11(4):450-9.
66. Li Y, Alsagabi M, Fan D, Bova GS, Tewfik AH, Dehm SM. (2011) Intragenic rearrangement and altered RNA splicing of the androgen receptor in a cell-based model of prostate cancer progression. Cancer Res. 2011;71(6):2108-17.
67. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. (2008) Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68(13):5469-77.
68. Zhau HY, Chang SM, Chen BQ, Wang Y, Zhang H, Kao C, et al. (1996) Androgen-repressed phenotype in human prostate cancer. Proc Natl Acad Sci U S A. 1996;93(26):15152-7.
69. Navone NM, Olive M, Ozen M, Davis R, Troncoso P, Tu SM, et al. (1997) Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clin Cancer Res. 1997;3(12 Pt 1):2493-500.
70. Navone NM, Rodriquez-Vargas MC, Benedict WF, Troncoso P, McDonnell TJ, Zhou JH, et al. (2000) TabBO: a model reflecting common molecular features of androgen-independent prostate cancer. Clin Cancer Res. 2000;6(3):1190-7.
71. Zhao XY, Boyle B, Krishnan AV, Navone NM, Peehl DM, Feldman D. (1999) Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a. J Urol. 1999;162(6):2192-9.
72. Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, et al. (2010) A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis. J Clin Invest. 2010;120(3):681-93.
73. Bello D, Webber MM, Kleinman HK, Wartinger DD, Rhim JS. (1997) Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. Carcinogenesis. 1997;18(6):1215-23.
74. Rhim JS, Webber MM, Bello D, Lee MS, Arnstein P, Chen LS, et al. (1994) Stepwise immortalization and transformation of adult human prostate epithelial cells by a combination of HPV-18 and v-Ki-ras. Proc Natl Acad Sci U S A. 1994;91(25):11874-8. PubMed PMID: 7991549;
75. Woodworth CD, Waggoner S, Barnes W, Stoler MH, DiPaolo JA. (1990) Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo. Cancer Res. 1990;50(12):3709-15.
76. Ellis WJ, Vessella RL, Buhler KR, Bladou F, True LD, Bigler SA, et al. (1996) Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23. Clin Cancer Res. 1996;2(6):1039-48.
77. Webber MM. (1979) Normal and benign human prostatic epithelium in culture. I. Isolation. In Vitro. 1979;15(12):967-82.
78. Webber MM, Trakul N, Thraves PS, Bello-DeOcampo D, Chu WW, Storto PD, et al. (1990) A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia. Carcinogenesis. 1999;20(7):1185-92.
79. Kosova F, TemeltaÅŸ G, Arı Z, Lekili M. (2014) Possible relations between oxidative damage and apoptosis in benign prostate hyperplasia and prostate cancer patients. Tumour Biol. 2014;35(5):4295-9.
80. Hayward SW, Dahiya R, Cunha GR, Bartek J, Deshpande N, Narayan P. (1995) Establishment and characterization of an immortalized but non-transformed human prostate epithelial cell line: BPH-1. In Vitro Cell Dev Biol Anim. 1995;31(1):14-24.
81. Jerde TJ, Wu Z, Theodorescu D, Bushman W. (2011) Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells. Prostate. 2011;71(8):791-800.
82. Myzak MC, Hardin K, Wang R, Dashwood RH, Ho E. (2006) Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis. 2006;27(4):811-9.
83. Lee M, Garkovenko E, Yun J, Weijerman P, Peehl D, Chen L, et al. (1994) Characterization of adult human prostatic epithelial-cells immortalized by polybrene-induced DNA transfection with a plasmid containing an origin-defective sv40-genome. Int J Oncol. 1994;4(4):821-30.
84. Brinkmann V, Foroutan H, Sachs M, Weidner KM, Birchmeier W. (1995) Hepatocyte growth factor/scatter factor induces a variety of tissue-specific morphogenic programs in epithelial cells. J Cell Biol. 1995;131(6 Pt 1):1573-86.
85. Chung LW, Huang WC, Sung SY, Wu D, Odero-Marah V, Nomura T, et al. (2006) Stromal-epithelial interaction in prostate cancer progression. Clin Genitourin Cancer. 2006;5(2):162-70.
86. Abate-Shen C, Shen MM. (2000) Molecular genetics of prostate cancer. Genes Dev. 2000;14(19):2410-34.
87. Weinberg DS, Weidner N. (1993) Concordance of DNA content between prostatic intraepithelial neoplasia and concomitant invasive carcinoma. Evidence that prostatic intraepithelial neoplasia is a precursor of invasive prostatic carcinoma. Arch Pathol Lab Med. 1993;117(11):1132-7.
88. Wang M, Liu A, Garcia FU, Rhim JS, Stearns ME. (1999) Growth of HPV-18 immortalized human prostatic intraepithelial neoplasia cell lines. Influence of IL-10, follistatin, activin-A, and DHT. Int J Oncol. 1999;14(6):1185-95.
89. Dunning WF. (1963) Prostate Cancer in the Rat. Natl Cancer Inst Monogr. 1963;12:351-69.
90. Axiak SM, Bigio A. (2012) Canine prostatic carcinoma. Compend Contin Educ Vet. 2012;34(10):E1-5.
91. Kasper S. (2005) Survey of genetically engineered mouse models for prostate cancer: analyzing the molecular basis of prostate cancer development, progression, and metastasis. J Cell Biochem. 2005;94(2):279-97.
92. Parisotto M, Metzger D. (2013) Genetically engineered mouse models of prostate cancer. Mol Oncol. 2013;7(2):190-205.
93. Hoehn W, Schroeder FH, Reimann JF, Joebsis AC, Hermanek P. (1980) Human prostatic adenocarcinoma: some characteristics of a serially transplantable line in nude mice (PC 82). Prostate. 1980;1(1):95-104.
94. van Weerden WM, Romijn JC. (2000) Use of nude mouse xenograft models in prostate cancer research. Prostate. 2000;43(4):263-71.
95. Wang Y, Revelo MP, Sudilovsky D, Cao M, Chen WG, Goetz L, et al. (2005) Development and characterization of efficient xenograft models for benign and malignant human prostate tissue. Prostate. 2005;64(2):149-59.
96. Stephenson RA, Dinney CP, Gohji K, Ordóñez NG, Killion JJ, Fidler IJ. (1992) Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst. 1992;84(12):951-7.
97. An Z, Wang X, Geller J, Moossa AR, Hoffman RM. (1998) Surgical orthotopic implantation allows high lung and lymph node metastatic expression of human prostate carcinoma cell line PC-3 in nude mice. Prostate. 1998;34(3):169-74.
98. Giavazzi R, Campbell DE, Jessup JM, Cleary K, Fidler IJ. Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinomas implanted into different sites in nude mice. Cancer Res. 1986;46(4 Pt 2):1928-33.
99. Gohji K, Nakajima M, Dinney C, Fan D, Pathak S, Killion J, et al. (1993) The importance of orthotopic implantation to the isolation and biological characterization of a metastatic human clear cell renal-carcinoma in nude-mice. Int J Oncol. 1993;2(1):23-32.
100. Naito S, von Eschenbach AC, Giavazzi R, Fidler IJ. (1986) Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986;46(8):4109-15.
101. Watahiki A, Wang Y, Morris J, Dennis K, O'Dwyer HM, Gleave M, et al. (2011) MicroRNAs associated with metastatic prostate cancer. PLoS One. 2011;6(9):e24950.
102. Xie N, Cheng H, Lin D, Liu L, Yang O, Jia L, et al. (2015) The expression of glucocorticoid receptor is negatively regulated by active androgen receptor signaling in prostate tumors. Int J Cancer. 2015;136(4):E27-38.
103. Lin D, Watahiki A, Bayani J, Zhang F, Liu L, Ling V, et al. (2008) ASAP1, a gene at 8q24, is associated with prostate cancer metastasis. Cancer Res. 2008;68(11):4352-9.
104. Lin D, Xue H, Wang Y, Wu R, Watahiki A, Dong X, et al. (2014) Next generation patient-derived prostate cancer xenograft models. Asian J Androl. 2014;16(3):407-12.
105. Living Tumour Laboratory. (2009) The Prostate Center at Vancouver General Hospital, British Columbia Cancer Research Center. Cited November 21, 2014. Available from
106. Lang SH, Sharrard RM, Stark M, Villette JM, Maitland NJ. (2001) Prostate epithelial cell lines form spheroids with evidence of glandular differentiation in three-dimensional Matrigel cultures. Br J Cancer. 2001;85(4):590-9.
107. Sieh S, Taubenberger AV, Rizzi SC, Sadowski M, Lehman ML, Rockstroh A, et al. (2012) Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment. PLoS One. 2012;7(9):e40217.
108. Greenberg NM, DeMayo F, Finegold MJ, Medina D, Tilley WD, Aspinall JO, et al. (1995) Prostate cancer in a transgenic mouse. Proc Natl Acad Sci U S A. 1995;92(8):3439-43.
109. Gingrich JR, Barrios RJ, Morton RA, Boyce BF, DeMayo FJ, Finegold MJ, et al. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 1996;56(18):4096-102.
110. Pollard M. (1973) Spontaneous prostate adenocarcinomas in aged germfree Wistar rats. J Natl Cancer Inst. 1973;51(4):1235-41.
111. Wilson EM, Viskochil DH, Bartlett RJ, Lea OA, Noyes CM, Petrusz P, et al. (1981) Model systems for studies on androgen-dependent gene expression in the rat prostate. Prog Clin Biol Res. 1981;75A:351-80.
112. Rennie PS, Bruchovsky N, Leco KJ, Sheppard PC, McQueen SA, Cheng H, et al. (1993) Characterization of two cis-acting DNA elements involved in the androgen regulation of the probasin gene. Mol Endocrinol. 1993;7(1):23-36.
113. DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, et al. (1988) SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell. 1988;54(2):275-83.
114. Gannon JV, Lane DP. (1987) p53 and DNA polymerase alpha compete for binding to SV40 T antigen. Nature. 1987;329(6138):456-8.
115. Bookstein R, Rio P, Madreperla SA, Hong F, Allred C, Grizzle WE, et al. (1990) Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc Natl Acad Sci U S A. 1990;87(19):7762-6.
116. Fan K, Dao DD, Schutz M, Fink LM. (1994) Loss of heterozygosity and overexpression of p53 gene in human primary prostatic adenocarcinoma. Diagn Mol Pathol. 1994;3(4):265-70.
117. Scherl A, Li JF, Cardiff RD, Schreiber-Agus N. (2004) Prostatic intraepithelial neoplasia and intestinal metaplasia in prostates of probasin-RAS transgenic mice. Prostate. 2004;59(4):448-59.
118. Song Z, Wu X, Powell WC, Cardiff RD, Cohen MB, Tin RT, et al. (2002) Fibroblast growth factor 8 isoform B overexpression in prostate epithelium: a new mouse model for prostatic intraepithelial neoplasia. Cancer Res. 2002;62(17):5096-105.
119. Shim EH, Johnson L, Noh HL, Kim YJ, Sun H, Zeiss C, et al. (2003) Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate. Cancer Res. 2003;63(7):1583-8.
120. Klezovitch O, Chevillet J, Mirosevich J, Roberts RL, Matusik RJ, Vasioukhin V. (2004) Hepsin promotes prostate cancer progression and metastasis. Cancer Cell. 2004;6(2):185-95.
121. Polnaszek N, Kwabi-Addo B, Peterson LE, Ozen M, Greenberg NM, Ortega S, et al. (2003) Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer. Cancer Res. 2003;63(18):5754-60.
122. Chiaverotti T, Couto SS, Donjacour A, Mao JH, Nagase H, Cardiff RD, et al. (2008) Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer. Am J Pathol. 2008;172(1):236-46.
123. di Sant'Agnese PA. (1992) Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer. 1992;70(1 Suppl):254-68.
124. Terry S, Beltran H. (2014) The many faces of neuroendocrine differentiation in prostate cancer progression. Front Oncol. 2014;4:60.
125. Kasper S, Sheppard PC, Yan Y, Pettigrew N, Borowsky AD, Prins GS, et al. (1998) Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer. Lab Invest. 1998;78(6):i-xv.
126. Masumori N, Thomas TZ, Chaurand P, Case T, Paul M, Kasper S, et al. (2001) A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res. 2001;61(5):2239-49.
127. Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, et al. (2003) Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003;4(3):223-38.
128. Ciuffreda L, Falcone I, Incani UC, Del Curatolo A, Conciatori F, Matteoni S, et al. (2014) PTEN expression and function in adult cancer stem cells and prospects for therapeutic targeting. Adv Biol Regul. 2014;56:66-80.
129. Abremski K, Hoess R. (1984) Bacteriophage P1 site-specific recombination. Purification and properties of the Cre recombinase protein. J Biol Chem. 1984;259(3):1509-14.
130. Kwak MK, Johnson DT, Zhu C, Lee SH, Ye DW, Luong R, et al. (2013) Conditional deletion of the Pten gene in the mouse prostate induces prostatic intraepithelial neoplasms at early ages but a slow progression to prostate tumors. PLoS One. 2013;8(1):e53476.
131. Wang S, Gao J, Lei Q, Rozengurt N, Pritchard C, Jiao J, et al. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell. 2003;4(3):209-21.
132. Li Q, Liu L, Zhang Q, Liu S, Ge D, You Z. (2014) Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells. Cancer Res Treat. 2014;46(3):297-306.
133. Zhang Q, Liu S, Xiong Z, Wang AR, Myers L, Melamed J, et al. (2014) Interleukin-17 promotes development of castration-resistant prostate cancer potentially through creating an immunotolerant and pro-angiogenic tumor microenvironment. Prostate. 2014;74(8):869-79.
134. Kwabi-Addo B, Giri D, Schmidt K, Podsypanina K, Parsons R, Greenberg N, et al. (2001) Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression. Proc Natl Acad Sci U S A. 2001;98(20):11563-8.
135. Kim MJ, Cardiff RD, Desai N, Banach-Petrosky WA, Parsons R, Shen MM, et al. (2002) Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc Natl Acad Sci U S A. 2002;99(5):2884-9.
136. 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. 2001;27(2):222-4.
137. Majumder PK, Yeh JJ, George DJ, Febbo PG, Kum J, Xue Q, et al. (2003) Prostate intraepithelial neoplasia induced by prostate restricted Akt activation: the MPAKT model. Proc Natl Acad Sci U S A. 2003;100(13):7841-6.
138. Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM, et al. (1999) Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A. 1999;96(5):2110-5.
139. Campbell JP, Merkel AR, Masood-Campbell SK, Elefteriou F, Sterling JA. (2012) Models of bone metastasis. J Vis Exp. 2012;(67):e4260.
140. Elkin M, Vlodavsky I. (2001) Tail vein assay of cancer metastasis. Curr Protoc Cell Biol. 2001;Chapter 19:Unit 19.2.
141. LeBeau AM, Sevillano N, Markham K, Winter MB, Murphy ST, Hostetter DR, et al. (2015) Imaging active urokinase plasminogen activator in prostate cancer. Cancer Res. 2015;75(7):1225-35.
142. Jenkins DE, Yu SF, Hornig YS, Purchio T, Contag PR. (2003) In vivo monitoring of tumor relapse and metastasis using bioluminescent PC-3M-luc-C6 cells in murine models of human prostate cancer. Clin Exp Metastasis. 2003;20(8):745-56.
143. Rucci N, Sanità P, Delle Monache S, Alesse E, Angelucci A. (2014) Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets. World J Clin Oncol. 2014;5(3):335-47.
144. Nandana S, Ellwood-Yen K, Sawyers C, Wills M, Weidow B, Case T, et al. (2010) Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse model. Prostate. 2010;70(6):591-600.
145. Valkenburg KC, Williams BO. (2011) Mouse models of prostate cancer. Prostate Cancer. 2011;2011:895238.
146. Abate-Shen C, Shen MM. (2002) Mouse models of prostate carcinogenesis. Trends Genet. 2002;18(5):S1-5.