Does prostate cancer co-opt the developmental program?

Differentiation

Volumn 76, Issue 6, 2008, Pages 736-744

  Marker, Paul C ^a  

^a UNIVERSITY OF WISCONSIN   (United States)

Author keywords

Androgen receptor; Epithelial mesenchymal interactions; ERG; ETS; Mutation; Nkx3.1; Prostate cancer; Prostate development; Pten; Stem cells

Indexed keywords

ANDROGEN; ANDROGEN RECEPTOR; ANDROSTANOLONE; CELL MARKER; TESTOSTERONE;

CANCER CELL; CANCER GROWTH; CARCINOGENESIS; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL RENEWAL; HORMONE ACTION; HUMAN; NONHUMAN; ORGANOGENESIS; PREDICTION; PRIORITY JOURNAL; PROSTATE; PROSTATE CANCER; PROSTATE EPITHELIUM; PROSTATIC INTRAEPITHELIAL NEOPLASIA; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; UROGENITAL SINUS; VALIDATION PROCESS;

EID: 47749145379     PISSN: 03014681     EISSN: 14320436     Source Type: Journal    
DOI: 10.1111/j.1432-0436.2008.00297.x     Document Type: Review

References (97)

1. Asatiani, E., Huang, W.X., Wang, A., Rodriguez Ortner, E., Cavalli, L.R., Haddad, B.R. Gelmann, E.P. (2005) Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer. Cancer Res 65 : 1164 1173.
2. Aumuller, G. Greenberg, J. (1976) Seasonal changes in the fine structure of the accessory sex gland in the mole (Talpa europaea). Cell Tissue Res 175 : 403 416.
3. Barclay, W.W., Woodruff, R.D., Hall, M.C. Cramer, S.D. (2005) A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer. Endocrinology 146 : 13 18.
4. Berman, D.M., Desai, N., Wang, X., Karhadkar, S.S., Reynon, M., Abate-Shen, C., Beachy, P.A. Shen, M.M. (2004) Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev Biol 267 : 387 398.
5. Bhatia-Gaur, R., Donjacour, A.A., Sciavolino, P.J., Kim, M., Desai, N., Young, P., Norton, C.R., Gridley, T., Cardiff, R.D., Cunha, G.R., Abate-Shen, C. Shen, M.M. (1999) Roles for Nkx3.1 in prostate development and cancer. Genes Dev 13 : 966 977.
6. Bowen, C., Bubendorf, L., Voeller, H.J., Slack, R., Willi, N., Sauter, G., Gasser, T.C., Koivisto, P., Lack, E.E., Kononen, J., Kallioniemi, O.P. Gelmann, E.P. (2000) Loss of NKX3.1 expression in human prostate cancers correlates with tumor progression. Cancer Res 60 : 6111 6115.
7. Brown, T.R., Lubahn, D.B., Wilson, E.M., Joseph, D.R., French, F.S. Migeon, C.J. (1988) Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: evidence for further genetic heterogeneity in this syndrome. Proc Natl Acad Sci USA 85 : 8151 8155.
8. Burger, H.G. (2002) Androgen production in women. Fertility and Sterility 77 (Suppl. 4) : S3 S5.
9. Burger, P.E., Xiong, X., Coetzee, S., Salm, S.N., Moscatelli, D., Goto, K. Wilson, E.L. (2005) Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue. Proc Natl Acad Sci USA 102 : 7180 7185.
10. Cairns, P., Okami, K., Halachmi, S., Halachmi, N., Esteller, M., Herman, J.G., Jen, J., Isaacs, W.B., Bova, G.S. Sidransky, D. (1997) Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57 : 4997 5000.
11. Cerveira, N., Ribeiro, F.R., Peixoto, A., Costa, V., Henrique, R., Jeronimo, C. Teixeira, M.R. (2006) TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia (New York, NY) 8 : 826 832.
12. Chang, C. Kokontis, J. (1988) Identification of a new member of the steroid receptor super-family by cloning and sequence analysis. Biochem Biophys Res Commun 155 : 971 977.
13. Charest, N.J., Zhou, Z.X., Lubahn, D.B., Olsen, K.L., Wilson, E.M. French, F.S. (1991) A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol Endocrinol 5 : 573 581.
14. Chen, C.D., Welsbie, D.S., Tran, C., Baek, S.H., Chen, R., Vessella, R., Rosenfeld, M.G. Sawyers, C.L. (2004) Molecular determinants of resistance to antiandrogen therapy. Nat Med 10 : 33 39.
15. Chesire, D.R. Isaacs, W.B. (2002) Ligand-dependent inhibition of beta-catenin/TCF signaling by androgen receptor. Oncogene 21 : 8453 8469.
16. Chipuk, J.E., Cornelius, S.C., Pultz, N.J., Jorgensen, J.S., Bonham, M.J., Kim, S.J. Danielpour, D. (2002) The androgen receptor represses transforming growth factor-beta signaling through interaction with Smad3. J Biol Chem 277 : 1240 1248.
17. Claessens, F., Alen, P., Devos, A., Peeters, B., Verhoeven, G. Rombauts, W. (1996) The androgen-specific probasin response element 2 interacts differentially with androgen and glucocorticoid receptors. J Biol Chem 271 : 19013 19016.
18. Collins, A.T., Berry, P.A., Hyde, C., Stower, M.J. Maitland, N.J. (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65 : 10946 10951.
19. Cunha, G.R. (2008) Mesenchymal - epithelial interactions: past, present, and future. Differentiation doi :.
20. Cunha, G.R. Lung, B. (1978) The possible influence of temporal factors in androgenic responsiveness of urogenital tissue recombinants from wild-type and androgen- insensitive (Tfm) mice. J Exp Zool 205 : 181 193.
21. Deslypere, J.P., Young, M., Wilson, J.D. McPhaul, M.J. (1992) Testosterone and 5 alpha-dihydrotestosterone interact differently with the androgen receptor to enhance transcription of the MMTV-CAT reporter gene. Mol Cell Endocrinol 88 : 15 22.
22. Doles, J., Cook, C., Shi, X., Valosky, J., Lipinski, R. Bushman, W. (2006) Functional compensation in Hedgehog signaling during mouse prostate development. Dev Biol 295 : 13 25.
23. Donjacour, A.A. Cunha, G.R. (1988) The effect of androgen deprivation on branching morphogenesis in the mouse prostate. Dev Biol 128 : 1 14.
24. Donjacour, A.A., Thomson, A.A. Cunha, G.R. (2003) FGF-10 plays an essential role in the growth of the fetal prostate. Dev Biol 261 : 39 54.
25. Edwards, J. Bartlett, J.M. (2005a) The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor. BJU Int 95 : 1320 1326.
26. Edwards, J. Bartlett, J.M. (2005b) The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen-receptor cofactors and bypass pathways. BJU Int 95 : 1327 1335.
27. Evans, G.S. Chandler, J.A. (1987) Cell proliferation studies in rat prostate. I. The proliferative role of basal and secretory epithelial cells during normal growth. Prostate 10 : 163 178.
28. Fan, L., Pepicelli, C.V., Dibble, C.C., Catbagan, W., Zarycki, J.L., Laciak, R., Gipp, J., Shaw, A., Lamm, M.L., Munoz, A., Lipinski, R., Thrasher, J.B. Bushman, W. (2004) Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology 145 : 3961 3970.
29. Freestone, S.H., Marker, P., Grace, O.C., Tomlinson, D.C., Cunha, G.R., Harnden, P. Thomson, A.A. (2003) Sonic hedgehog regulates prostatic growth and epithelial differentiation. Dev Biol 264 : 352 362.
30. Gaspar, M.L., Meo, T., Bourgarel, P., Guenet, J.L. Tosi, M. (1991) A single base deletion in the Tfm androgen receptor gene creates a short-lived messenger RNA that directs internal translation initiation. Proc Natl Acad Sci USA 88 : 8606 8610.
31. Gioeli, D. (2005) Signal transduction in prostate cancer progression. Clin Sci (Lond) 108 : 293 308.
32. Goeritz, F., Quest, M., Wagener, A., Fassbender, M., Broich, A., Hildebrandt, T.B., Hofmann, R.R. Blottner, S. (2003) Seasonal timing of sperm production in roe deer: interrelationship among changes in ejaculate parameters, morphology and function of testis and accessory glands. Theriogenology 59 : 1487 1502.
33. Greaves, M.F., Hariri, G., Newman, R.A., Sutherland, D.R., Ritter, M.A. Ritz, J. (1983) Selective expression of the common acute lymphoblastic leukemia (gp 100) antigen on immature lymphoid cells and their malignant counterparts. Blood 61 : 628 639.
34. Gu, G., Yuan, J., Wills, M. Kasper, S. (2007) Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 67 : 4807 4815.
35. Hammond, G.L. (1978) Endogenous steroid levels in the human prostate from birth to old age: a comparison of normal and diseased tissues. J Endocrinol 78 : 7 19.
36. He, W.W., Kumar, M.V. Tindall, D.J. (1991) A frameshift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Res 19 : 2373 2378.
37. He, W.W., Sciavolino, P.J., Wing, J., Augustus, M., Hudson, P., Meissner, P.S., Curtis, R.T., Shell, B.K., Bostwick, D.G., Tindall, D.J., Gelmann, E.P., Abate-Shen, C. Carter, K.C. (1997) A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer. Genomics 43 : 69 77.
38. Ho, K.C., Quarmby, V.E., French, F.S. Wilson, E.M. (1992) Molecular cloning of rat prostate transglutaminase complementary DNA. The major androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland. J Biol Chem 267 : 12660 12667.
39. Hudson, D.L., O'Hare, M., Watt, F.M. Masters, J.R. (2000) Proliferative heterogeneity in the human prostate. Laboratory investigation: evidence for epithelial stem cells. J Tech Methods Pathol 80 : 1243 1250.
40. Huggins, C. Hodges, C.V. (1941) Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1 : 293 297.
41. Hurt, E.M., Kawasaki, B.T., Klarmann, G.J., Thomas, S.B. Farrar, W.L. (2008) CD44(+)CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Brit J Cancer 98 : 756 765.
42. Joesting, M.S., Cheever, T.R., Volzing, K.G., Yamaguchi, T., Wolf, V., Naf, D., Rubin, J.S. Marker, P.C. (2008) Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate. Dev Biol 317 : 161 173.
43. Joesting, M.S., Perrin, S., Elenbaas, B., Fawell, S.E., Rubin, J.S., Franco, O.E., Hayward, S.W., Cunha, G.R. Marker, P.C. (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65 : 10423 10430.
44. Jost, A. (1953) Problems of fetal endocrinology: gonadal and hypophyseal hormones. Recent Prog Horm Res 8 : 390 418.
45. Jost, A. (1972) A new look at the mechanisms controlling sex differentiation in mammals. Johns Hopkins Med J 130 : 38 53.
46. Karhadkar, S.S., Bova, G.S., Abdallah, N., Dhara, S., Gardner, D., Maitra, A., Isaacs, J.T., Berman, D.M. Beachy, P.A. (2004) Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 431 : 707 712.
47. Kim, M.J., Bhatia-Gaur, R., Banach-Petrosky, W.A., Desai, N., Wang, Y., Hayward, S.W., Cunha, G.R., Cardiff, R.D., Shen, M.M. Abate-Shen, C. (2002a) Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis. Cancer Res 62 : 2999 3004.
48. Kim, M.J., Cardiff, R.D., Desai, N., Banach-Petrosky, W.A., Parsons, R., Shen, M.M. Abate-Shen, C. (2002b) Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc Natl Acad Sci USA 99 : 2884 2889.
49. Klezovitch, O., Risk, M., Coleman, I., Lucas, J.M., Null, M., True, L.D., Nelson, P.S. Vasioukhin, V. (2008) A causal role for ERG in neoplastic transformation of prostate epithelium. Proc Natl Acad Sci USA 105 : 2105 2110.
50. Kurita, T., Wang, Y.Z., Donjacour, A.A., Zhao, C., Lydon, J.P., O'Malley, B.W., Isaacs, J.T., Dahiya, R. Cunha, G.R. (2001) Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death and Differ 8 : 192 200.
51. Kwong, J., Xuan, J.W., Chan, P.S., Ho, S.M. Chan, F.L. (2000) A comparative study of hormonal regulation of three secretory proteins (prostatic secretory protein-PSP94, probasin, and seminal vesicle secretion II) in rat lateral prostate. Endocrinology 141 : 4543 4551.
52. Lamm, M.L., Catbagan, W.S., Laciak, R.J., Barnett, D.H., Hebner, C.M., Gaffield, W., Walterhouse, D., Iannaccone, P. Bushman, W. (2002) Sonic hedgehog activates mesenchymal Gli1 expression during prostate ductal bud formation. Dev Biol 249 : 349 366.
53. Lawson, D.A., Xin, L., Lukacs, R.U., Cheng, D. Witte, O.N. (2007) Isolation and functional characterization of murine prostate stem cells. Proc Natl Acad Sci USA 104 : 181 186.
54. Lei, Q., Jiao, J., Xin, L., Chang, C.J., Wang, S., Gao, J., Gleave, M.E., Witte, O.N., Liu, X. Wu, H. (2006) NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss. Cancer Cell 9 : 367 378.
55. Leong, K.G. Gao, W.-Q. (2008) The Notch pathway in prostate development and cancer. Differentiation doi :.
56. Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S.I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., Bigner, S.H., Giovanella, B.C., Ittmann, M., Tycko, B., Hibshoosh, H., Wigler, M.H. Parsons, R. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275 : 1943 1947.
57. Linja, M.J., Savinainen, K.J., Saramaki, O.R., Tammela, T.L., Vessella, R.L. Visakorpi, T. (2001) Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 61 : 3550 3555.
58. Litman, H.J., Bhasin, S., Link, C.L., Araujo, A.B. McKinlay, J.B. (2006) Serum androgen levels in black, Hispanic, and white men. J Clin Endocrinol Metab 91 : 4326 4334.
59. Lubahn, D.B., Brown, T.R., Simental, J.A., Higgs, H.N., Migeon, C.J., Wilson, E.M. French, F.S. (1989) Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci USA 86 : 9534 9538.
60. Lubahn, D.B., Joseph, D.R., Sullivan, P.M., Willard, H.F., French, F.S. Wilson, E.M. (1988) Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 240 : 327 330.
61. Lyon, M.F. Hawkes, S.G. (1970) X-linked gene for testicular feminization in the mouse. Nature 227 : 1217 1219.
62. Mahendroo, M.S., Cala, K.M., Hess, D.L. Russell, D.W. (2001) Unexpected virilization in male mice lacking steroid 5 alpha-reductase enzymes. Endocrinology 142 : 4652 4662.
63. Memarzadeh, S., Xin, L., Mulholland, D.J., Mansukhani, A., Wu, H., Teitell, M.A. Witte, O.N. (2007) Enhanced paracrine FGF10 expression promotes formation of multifocal prostate adenocarcinoma and an increase in epithelial androgen receptor. Cancer Cell 12 : 572 585.
64. Mills, J.S., Needham, M. Parker, M.G. (1987) Androgen regulated expression of a spermine binding protein gene in mouse ventral prostate. Nucleic Acids Res 15 : 7709 7724.
65. Morris, J.M. (1953) The syndrome of testicular feminization in male pseudohermaphrodites. Am J Obstet Gynec 65 : 1192 1211.
66. Mulholland, D.J., Cheng, H., Reid, K., Rennie, P.S. Nelson, C.C. (2002) The androgen receptor can promote beta-catenin nuclear translocation independently of adenomatous polyposis coli. J Biol Chem 277 : 17933 17943.
67. Nusse, R. (2003) Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface. Development 130 : 5297 5305.
68. Olumi, A.F., Grossfeld, G.D., Hayward, S.W., Carroll, P.R., Tlsty, T.D. Cunha, G.R. (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59 : 5002 5011.
69. Pierce, G.B., Nakane, P.K., Martinez-Hernandez, A. Ward, J.M. (1977) Ultrastructural comparison of differentiation of stem cells of murine adenocarcinomas of colon and breast with their normal counterparts. J Natl Cancer Inst 58 : 1329 1345.
70. Pierce, G.B. Speers, W.C. (1988) Tumors as caricatures of the process of tissue renewal: prospects for therapy by directing differentiation. Cancer Res 48 : 1996 2004.
71. Pierce, G.B. Wallace, C. (1971) Differentiation of malignant to benign cells. Cancer Res 31 : 127 134.
72. Podlasek, C.A., Barnett, D.H., Clemens, J.Q., Bak, P.M. Bushman, W. (1999) Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium. Dev Biol 209 : 28 39.
73. Pointis, G., Latreille, M.T. Cedard, L. (1980) Gonado-pituitary relationships in the fetal mouse at various times during sexual differentiation. J Endocrinol 86 : 483 488.
74. Pratt, W.B. Toft, D.O. (2003) Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Exp Biol Med 228 : 111 133.
75. Pritchard, C.C. Nelson, P.S. (2008) Gene expression profiling in the developing prostate. Differentiation doi :.
76. Rahman, M., Miyamoto, H. Chang, C. (2004) Androgen receptor coregulators in prostate cancer: mechanisms and clinical implications. Clin Cancer Res 10 : 2208 2219.
77. Riegman, P.H., Vlietstra, R.J., van der Korput, J.A., Brinkmann, A.O. Trapman, J. (1991) The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol Endocrinol 5 : 1921 1930.
78. Russell, D.W. Wilson, J.D. (1994) Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem 63 : 25 61.
79. Sanchez, P., Hernandez, A.M., Stecca, B., Kahler, A.J., DeGueme, A.M., Barrett, A., Beyna, M., Datta, M.W., Datta, S. Ruiz i Altaba, A. (2004) Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 101 : 12561 12566.
80. Schuur, E.R., Henderson, G.A., Kmetec, L.A., Miller, J.D., Lamparski, H.G. Henderson, D.R. (1996) Prostate-specific antigen expression is regulated by an upstream enhancer. J Biol Chem 271 : 7043 7051.
81. Shi, X., Gipp, J. Bushman, W. (2007) Anchorage-independent culture maintains prostate stem cells. Dev Biol 312 : 396 406.
82. Singh, U.P. (1997) Reproductive biology of the male sheath-tailed bat, Taphozous longimanus (Emballonuridae) from India. Biomed Environ Sci 10 : 14 26.
83. Takeda, H., Lasnitzki, I. Mizuno, T. (1986) Analysis of prostatic bud induction by brief androgen treatment in the fetal rat urogenital sinus. J Endocrinol 110 : 467 470.
84. Tenenholz, T.C., Shields, C., Ramesh, V.R., Tercilla, O. Hagan, M.P. (2007) Survival benefit for early hormone ablation in biochemically recurrent prostate cancer. Urologic Oncol 25 : 101 109.
85. Tomlins, S.A., Laxman, B., Varambally, S., Cao, X., Yu, J., Helgeson, B.E., Cao, Q., Prensner, J.R., Rubin, M.A., Shah, R.B., Mehra, R. Chinnaiyan, A.M. (2008) Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia 10 : 177 188.
86. Tomlins, S.A., Mehra, R., Rhodes, D.R., Smith, L.R., Roulston, D., Helgeson, B.E., Cao, X., Wei, J.T., Rubin, M.A., Shah, R.B. Chinnaiyan, A.M. (2006) TMPRSS2: ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res 66 : 3396 3400.
87. Tomlins, S.A., Rhodes, D.R., Perner, S., Dhanasekaran, S.M., Mehra, R., Sun, X.W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R., Lee, C., Montie, J.E., Shah, R.B., Pienta, K.J., Rubin, M.A. Chinnaiyan, A.M. (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310 : 644 648.
88. Trotman, L.C., Niki, M., Dotan, Z.A., Koutcher, J.A., Di Cristofano, A., Xiao, A., Khoo, A.S., Roy-Burman, P., Greenberg, N.M., Van Dyke, T., Cordon-Cardo, C. Pandolfi, P.P. (2003) Pten dose dictates cancer progression in the prostate. PLoS Biol 1 : E59.
89. Tsujimura, A., Koikawa, Y., Salm, S., Takao, T., Coetzee, S., Moscatelli, D., Shapiro, E., Lepor, H., Sun, T.T. Wilson, E.L. (2002) Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J Cell Biol 157 : 1257 1265.
90. Wang, B.E., Shou, J., Ross, S., Koeppen, H., De Sauvage, F.J. Gao, W.Q. (2003a) Inhibition of epithelial ductal branching in the prostate by sonic hedgehog is indirectly mediated by stromal cells. J Biol Chem 278 : 18506 18513.
91. Wang, S., Gao, J., Lei, Q., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G.V., Li, G., Roy-Burman, P., Nelson, P.S., Liu, X. Wu, H. (2003b) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4 : 209 221.
92. Wang, S., Garcia, A.J., Wu, M., Lawson, D.A., Witte, O.N. Wu, H. (2006) Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci USA 103 : 1480 1485.
93. Wu, C.T., Altuwaijri, S., Ricke, W.A., Huang, S.P., Yeh, S., Zhang, C., Niu, Y., Tsai, M.Y. Chang, C. (2007) Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor. Proc Natl Acad Sci USA 104 : 12679 12684.
94. Xin, L., Lukacs, R.U., Lawson, D.A., Cheng, D. Witte, O.N. (2007) Self-renewal and multilineage differentiation in vitro from murine prostate stem cells. Stem Cells (Dayton, Ohio) 25 : 2760 2769.
95. Yang, F., Li, X., Sharma, M., Sasaki, C.Y., Longo, D.L., Lim, B. Sun, Z. (2002) Linking beta-catenin to androgen-signaling pathway. J Biol Chem 277 : 11336 11344.
96. Zhou, Z., Flesken-Nikitin, A., Corney, D.C., Wang, W., Goodrich, D.W., Roy-Burman, P. Nikitin, A.Y. (2006) Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res 66 : 7889 7898.
97. Zhou, Z., Flesken-Nikitin, A. Nikitin, A.Y. (2007) Prostate cancer associated with p53 and Rb deficiency arises from the stem/progenitor cell-enriched proximal region of prostatic ducts. Cancer Res 67 : 5683 5690.