Skip to main content
SpringerLink
Log in

Transgenic Mouse Models for Prostate Cancer

Identification of an Androgen-Dependent Promoter and Creation and Characterization of the Long Probasin Promoter-Large T Antigen (LPB-Tag) Model

  • Protocol
Prostate Cancer Methods and Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 81))

Abstract

An appropriate model to study the complex process of prostate tumorigenesis needs to reflect at least some aspects of the human disease presented in the clinic. The progression of prostate cancer includes the development of high-grade prostatic intraepithelial neoplasia (HGPIN, the precursor lesion for usual peripheral zone prostate cancer) (1), invasion, growth and potential dedifferentiation of organ confined tumor (2), extension outside of the prostate (either before or after local therapy), development of metastasis, and the progression from androgen-dependent (AD) to androgen-independent (AI) disease (3). Clinical observations have shown that androgen withdrawal has the greatest impact on the development and progression of prostate cancer. Therefore, androgen deprivation has been the gold standard in treating patients who have advanced prostate cancer (4,5). More than 80% of such patients show a favorable response, as evidenced by a decrease in serum prostate-specific antigen (PSA) levels and tumor regression, but tumor growth could resume despite continuous treatment (6). Although the progressive development of AI is poorly understood, the androgen receptor (AR) appears to be pivotal in the progression from AD to AI prostate cancer. Four possible mechanisms by which the AR may be actively involved in the development of AI include (1) mutations in the AR (5,7–11); (2) AR amplification (12,13); (3) ligand-independent activation of AR through other signaling pathways (14–22); and (4) altered activity of AR coregulators (either co-activators or co-inhibitors) (22–24).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bostwick, D. G. (1996) Prospective origins of prostate carcinoma. Prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia (review). Cancer 78, 330–336.

    Article  PubMed  CAS  Google Scholar 

  2. Greene, D. R., Wheeler, T. M., Egawa, S., Dunn, J. K., and Scardino, P. T. (1991) A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate. J. Urol. 146, 1069–1076.

    PubMed  CAS  Google Scholar 

  3. Wilding, G. (1992) The importance of steroid hormones in prostate cancer. Cancer Surv. 14, 113–130.

    PubMed  CAS  Google Scholar 

  4. Brewster, S. F. and Simons, J. W. (1994) Gene therapy in urological oncology: principles, strategies and potential. Eur. Urol. 25, 177–182.

    PubMed  CAS  Google Scholar 

  5. Taplin, M. E., Bubley, G. J., Shuster, T. D., Frantz, M. E., Spooner, A. E., Ogata, G. K., et al. (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer (see comments). N. Engl. J. Med. 332, 1393–1398.

    Article  PubMed  CAS  Google Scholar 

  6. Kelly, W. K. and Scher, H. I. (1993) Prostate specific antigen decline after antian-drogen withdrawal: the flutamide withdrawal syndrome. J. Urol. 149, 607–609.

    PubMed  CAS  Google Scholar 

  7. Bentel, J. M. and Tilley, W. D. (1996) Androgen receptors in prostate cancer. J. Endocrinol. 151, 1–11.

    Article  PubMed  CAS  Google Scholar 

  8. Reid, P., Kantoff, P., and Oh, W. (1999) Antiandrogens in prostate cancer. Invest. New Drugs 17, 271–284.

    Article  PubMed  CAS  Google Scholar 

  9. Buchanan, G., Yang, M., Harris, J. M., Nahm, H. S., Han, G., Moore, N., et al. (2001) Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function. Mol. Endocrinol. 15, 46–56.

    Article  PubMed  CAS  Google Scholar 

  10. Giovannucci, E., Stampfer, M. J., Krithivas, K., Brown, M., Dahl, D., Brufsky, A., et al. (1997) The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl. Acad. Sci. USA 94, 3320–3323.

    Article  PubMed  CAS  Google Scholar 

  11. Irvine, R. A., Yu, M. C., Ross, R. K., and Coetzee, G. A. (1995) The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. Cancer Res. 55, 1937–1940.

    PubMed  CAS  Google Scholar 

  12. Koivisto, P., Kononen, J., Palmberg, C., Tammela, T., Hyytinen, E., Isola, J., et al. (1997) Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 57, 314–319.

    PubMed  CAS  Google Scholar 

  13. Miyoshi, Y., Uemura, H., Fujinami, K., Mikata, K., Harada, M., Kitamura, H., et al. (2001) Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients. Prostate 43, 225–232.

    Article  Google Scholar 

  14. Gregory, C. W., Hamil, K. G., Kim, D., Hall, S. H., Pretlow, T. G., Mohler, J. L., et al. (1998) Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes. Cancer Res. 58, 5718–5724.

    PubMed  CAS  Google Scholar 

  15. Chen S-y, Wang, J., Yu G, Liu, W., and Pearce, D. (1997) Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity. J. Biol. Chem. 272, 14087–14092.

    Article  PubMed  CAS  Google Scholar 

  16. Ruijter, E., Van De Kaa, C., Miller, G., Ruiter, D., Debruyne, F., and Schalken, J. (1999) Molecular genetics and epidemiology of prostate carcinoma. Endocr. Rev. 20, 22–45.

    Article  PubMed  CAS  Google Scholar 

  17. Craft, N., Shostak, Y., Carey, M., and Sawyers, C. (1999) A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat. Med. 5, 280–285.

    Article  PubMed  CAS  Google Scholar 

  18. Yeh, S., Lin, H. K., Kang, H. Y., Thin, T. H., Lin, M. F., and Chang, C. (1999) From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc. Natl. Acad. Sci. USA. 96, 5458–5463.

    Article  PubMed  CAS  Google Scholar 

  19. Wen, Y., Hu, M. C., Makino, K., Spohn, B., Bartholomeusz, G., Yan, D. H., et al. (2000) HER-2/neu promotes androgen-independent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res. 60, 6841–6845.

    PubMed  CAS  Google Scholar 

  20. Rajah, R., Valentinis, B., and Cohen, P. (1997) Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53-and IGF-independent mechanism. J. Biol. Chem. 272, 12181–12188.

    Article  PubMed  CAS  Google Scholar 

  21. Hayes S. A., Zarnegar, M., Sharma, M., Yang, F., Peehl, D. M., ten Dijke P., et al. (2001) SMAD3 represses androgen receptor-mediated transcription. Cancer Res. 61, 2112–2118.

    PubMed  CAS  Google Scholar 

  22. Kang, H. Y., Lin, H. K., Hu, Y. C., Yeh, S., Huang, K. E., and Chang, C. (2001) From transforming growth factor-beta signaling to androgen action: Identification of Smad3 as an androgen receptor coregulator in prostate cancer cells. Proc. Natl. Acad. Sci. USA. 98, 3018–3023.

    Article  PubMed  CAS  Google Scholar 

  23. Fujimoto, N., Yeh, S., Kang, H. Y., Inui, S., Chang, H. C., Mizokami, A., et al. (1999) Cloning and characterization of androgen receptor coactivator, ARA55, in human prostate. J. Biol. Chem. 274, 8316–8321.

    Article  PubMed  CAS  Google Scholar 

  24. Kang, H. Y., Yeh, S., Fujimoto, N., and Chang, C. (1999) Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor. J. Biol. Chem. 274, 8570–8576.

    Article  PubMed  CAS  Google Scholar 

  25. de Pinieux, G., Legrier, M. E., Poirson-Bichat, F., Courty, Y., Bras-Goncalves, R., Dutrillaux, A. M., et al. (2001) Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach. Am. J. Pathol. 159, 753–764.

    Article  PubMed  Google Scholar 

  26. Gregory, C. W., Kim, D., Ye, P., D’Ercole, A. J., Pretlow, T. G., Mohler, J. L., et al. (1999) Androgen receptor up-regulates insulin-like growth factor binding protein-5 (IGFBP-5) expression in a human prostate cancer xenograft. Endocrinology 140, 2372–2381.

    Article  PubMed  CAS  Google Scholar 

  27. Nickerson, T., Chang, F., Lorimer, D., Smeekens, S. P., Sawyers, C. L., and Pol-lak, M. (2001) In vivo progression of lapc-9 and lncap prostate cancer models to androgen independence is associated with increased expression of insulin-like growth factor i (igf-i) and igf-i receptor (igf-ir). Cancer Res. 61, 6276–6280.

    PubMed  CAS  Google Scholar 

  28. Zhau, H. E., Li, C. L., and Chung, L. W. (2000) Establishment of human prostate carcinoma skeletal metastasis models. Cancer 88, 2995–3001.

    Article  PubMed  CAS  Google Scholar 

  29. Korenchuk, S., Lehr, J. E., MClean, L., Lee, Y. G., Whitney, S., Vessella, R., et al. (2001) VCaP, a cell-based model system of human prostate cancer. In Vivo 15, 163–168.

    PubMed  CAS  Google Scholar 

  30. Navone, N. M., Logothetis, C. J., von Eschenbach, A. C., and Troncoso, P. (1998) Model systems of prostate cancer: uses and limitations. Cancer Metastasis Rev. 17, 361–371.

    Article  PubMed  Google Scholar 

  31. van Weerden, W. M. and Romijn, J.C. (2000) Use of nude mouse xenograft models in prostate cancer research. Prostate 43, 263–271.

    Article  PubMed  Google Scholar 

  32. Bostwick, D. G., Ramnani, D., and Qian, J. (2000) Prostatic intraepithelial neoplasia: Animal models 2000. Prostate 43, 286–294.

    Article  PubMed  CAS  Google Scholar 

  33. Waters, D. J., Bostwick, D. G., and Murphy, G. P. (1998) Conference summary: First International Workshop on Animal models of Prostate Cancer. Prostate 36, 47–48.

    Article  PubMed  CAS  Google Scholar 

  34. Barrios, R., Lebovitz, R. M., Wiseman, A. L., Weisoly, D. L., Matusik, R. J., DeMayo, F., et al. (1996) RasT24 driven by a probasin promoter induces prostatic hyperplasia in transgenic mice. Transgenics 2, 23–28.

    CAS  Google Scholar 

  35. Voelkel-Johnson, C., Voeks, D. J., Greenberg, N. M., Barrios, R., Maggouta, F., Kurtz, D. T., et al.(2000) Genomic instability-based transgenic models of prostate cancer. Carcinogenesis 21, 1623–1627.

    Article  PubMed  CAS  Google Scholar 

  36. Shibata, M. A., Maroulakou, I. G., Jorcyk, C. L., Gold, L. G., Ward, J. M., and Green, J. E. (1996) p53-independent apoptosis during mammary tumor progression in C3(1)/SV40 large T antigen transgenic mice: Auppression of apoptosis during the transition from preneoplasia to carcinoma. Cancer Res. 56, 2998–3003.

    PubMed  CAS  Google Scholar 

  37. Kitsberg, D. I. and Leder, P. (1996) Keratinocyte growth factor induces mammary and prostatic hyperplasia and mammary adenocarcinoma in transgenic mice. Oncogene 13, 2507–2515.

    PubMed  CAS  Google Scholar 

  38. Hennighausen, L., McKnight, R., Burdon, T., Baik, M., Wall, R. J., and Smith, G. H. (1994) Whey acidic protein extrinsically expressed from the mouse mammary tumor virus long terminal repeat results in hyperplasia of the coagulation gland epithelium and impaired mammary development. Cell Growth Differ. 5, 607–613.

    PubMed  CAS  Google Scholar 

  39. DiGiovanni, J., Kiguchi, K., Frijhoff, A., Wilker, E., Bol, D. K., Beltran, L., et al. (2000) Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc. Natl. Acad. Sci. USA 97, 3455–3460.

    Article  PubMed  CAS  Google Scholar 

  40. Greenberg, N. M., DeMayo, F. J., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O., et al. (1995) Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA. 92, 3439–3443.

    Article  PubMed  CAS  Google Scholar 

  41. Gingrich, J. R., Barrios, R. J., Morton, R. A., Boyce, B. F., DeMayo, F. J., Fine-gold, M. J., et al. (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096–4102.

    PubMed  CAS  Google Scholar 

  42. Kasper, S., Sheppard, P. C., Yan, Y., Pettigrew, N., Borowsky, A. D., Prins, G. S., et al. (1998) Development, progression and androgen-dependence of prostate tumors in transgenic: A model for prostate cancer. Lab. Invest. 78, 319–334.

    PubMed  CAS  Google Scholar 

  43. Masumori, N., Thomas, T. Z., Case, T., Paul, M., Kasper, S., Chaurand, P., et al. (2001) A probasin-large T antigen transgenic mouse line develops prostate adeno and neuroendocrine carcinoma with metastatic potential. Cancer Res. 61, 2239–2249.

    PubMed  CAS  Google Scholar 

  44. Tehranian, A., Morris, D. W., Min, B. H., Bird, D. J., Cardiff, R. D., and Barry, P. A. (1996) Neoplastic transformation of prostatic and urogenital epithelium by the polyoma virus middle T gene. Am. J. Pathol. 149, 1177–1191.

    PubMed  CAS  Google Scholar 

  45. Garabedian, E. M., Humphrey, P. A., and Gordon, J. I. (1998) A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc. Natl. Acad. Sci. USA. 95, 15382–15387.

    Article  PubMed  CAS  Google Scholar 

  46. Perez-Stable, C., Altman, N. H., Brown, J., Harbison, M., Cray, C., and Roos, B. A. (1996) Prostate, adrenocortical, and brown adispose tumors in fetal globin T antigen transgenic mice. Lab. Invest. 74, 363–373.

    PubMed  CAS  Google Scholar 

  47. Skalnik, D. G., Dorfman, D. M., Williams, D. A., and Orkin, S. H. (1991) Restriction of neuroblastoma to the prostate gland in transgenic mice. Mol. Cell. Biochem. 11, 4518–4527.

    CAS  Google Scholar 

  48. Pipas, J. M. and Levine, A. J. (2001) Role of T antigen interactions with p53 in tumorigenesis. Semin. Cancer Biol. 11, 23–30.

    Article  PubMed  CAS  Google Scholar 

  49. Ali, S. H. and Decaprio, J. A. (2001) Cellular transformation by SV40 large T antigen: Interaction with host proteins. Semin. Cancer Biol. 11, 15–23.

    Article  PubMed  CAS  Google Scholar 

  50. Rundell, K. and Parakati, R. (2001) The role of the SV40 ST antigen in cell growth promotion and transformation. Semin. Cancer Biol. 11, 5–13.

    Article  PubMed  CAS  Google Scholar 

  51. Myers, R. B., Oelschlager, D., Srivastava, S., and Grizzle, W. E. (1994) Accumulation of the p53 protein occurs more frequently in metastatic than in localized prostatic adenocarcinomas. Prostate 25, 243–248.

    Article  PubMed  CAS  Google Scholar 

  52. Bookstein, R., Rio, P., Madreperla, S. A., Hong, F., Allred, C., Grizzle, W. E., et al. (1990) Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc. Natl. Acad. Sci. USA. 87, 7762–7766.

    Article  PubMed  CAS  Google Scholar 

  53. Bookstein, R., Shew, J. Y., Chen, P. L., Scully, P., and Lee, W. H. (1990) Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247, 712–715.

    Article  PubMed  CAS  Google Scholar 

  54. Bookstein, R., MacGrogan, D., Hilsenbeck, S. G., Sharkey, F., and Allred, D. C. (1993) p53 is mutated in a subset of advanced-stage prostate cancers. Cancer Res. 53, 3369–3373.

    PubMed  CAS  Google Scholar 

  55. Jasani, B., Cristaudo, A., Emri, S. A., Gazdar, A. F., Gibbs, A., Krynska, B., et al. (2001) Association of SV40 with human tumours. Semin. Cancer Biol. 11, 49–61.

    Article  PubMed  CAS  Google Scholar 

  56. Shibata, M. A., Ward, J. M., Devor, D. E., Liu, M. L., and Green, J. E. (1996) Progression of prostatic intraepithelial neoplasia to invasive carcinoma in C3(1)/SV40 large T antigen transgenic mice: Histopathological and molecular biological alterations. Cancer Res. 56, 4894–4903.

    PubMed  CAS  Google Scholar 

  57. Huss, W. J., Hanrahan, C. F., Barrios, R. J., Simons, J. W., and Greenberg, N. M. (2001) Angiogenesis and prostate cancer: identification of a molecular progression switch. Cancer Res. 61, 2736–2743.

    PubMed  CAS  Google Scholar 

  58. Charest, N. J., Zhou, Z. X., Lubahn, D. B., Olsen, K. L., Wilson, E. M., and French, F. S. (1991) A frameshift mutation destabilizes androgen receptor messenger RNA in the Tfm mouse. Mol. Endocrinol. 5, 573–581.

    Article  PubMed  CAS  Google Scholar 

  59. He, W. W., Kumar, M. V., and Tindall, D. J.(1991) A frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse. Nucleic Acids Res. 19, 2373–2378.

    Article  PubMed  CAS  Google Scholar 

  60. Cunha, G. R. and 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.

    Article  PubMed  CAS  Google Scholar 

  61. Cunha, G. R. and Chung, L. W. (1981) Stromal-epithelial interactions—I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J. Steroid Biochem. 14, 1317–1324.

    Article  PubMed  CAS  Google Scholar 

  62. Zheng, B., Mills, A. A., and Bradley, A. (1999) A system for rapid generation of coat color-tagged knockouts and defined chromosomal rearrangements in mice. Nucleic Acids Res. 27, 2354–2360.

    Article  PubMed  CAS  Google Scholar 

  63. Hertzog, P. J. and Kola, I. (2001) Overview. Gene knockouts. Methods Mol. Biol. 158, 1–10.

    PubMed  CAS  Google Scholar 

  64. Eddy, E. M., Washburn, T. F., Bunch, D. O., Goulding, E. H., Gladen, B. C., Lubahn, D. B., et al. (1996) Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility. Endocrinology 137, 4796–4805.

    Article  PubMed  CAS  Google Scholar 

  65. Risbridger, G. P., Wang, H., Frydenberg, M., and Cunha, G. (2001) The metaplastic effects of estrogen on mouse prostate epithelium: Proliferation of cells with basal cell phenotype. Endocrinology 142, 2443–2450.

    Article  PubMed  CAS  Google Scholar 

  66. Colombel, M., Radvanyi, F., Blanche, M., Abbou, C., Buttyan, R., Donehower, L. A., et al. (1995) Androgen suppressed apoptosis is modified in p53 deficient mice. Oncogene 10, 1269–1274.

    PubMed  CAS  Google Scholar 

  67. Di Cristofano, A., De Acetis, M., Koff, A., Cordon-Cardo, C., and Pandolfi, P. P. (1998) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat. Genet. 27, 134–135.

    Google Scholar 

  68. Luo, J. L., Yang, Q., Tong, W. M., Hergenhahn, M., Wang, Z. Q., and Hollstein, M. (2001) Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool. Oncogene 20, 320–328.

    Article  PubMed  CAS  Google Scholar 

  69. Wang, Y., Hayward, S. W., Donjacour, A. A., Young, P., Jacks, T., Sage, J., et al. (2000) Sex hormone-induced carcinogenesis in Rb-deficient prostate tissue. Cancer Res. 60, 6008–6017.

    PubMed  CAS  Google Scholar 

  70. Sauer, B. (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14, 381–392.

    Article  PubMed  CAS  Google Scholar 

  71. Wu, X., Wu, J., Huang, J., Powell, W. C., Zhang, J., Matusik, R. J., et al. (2001) Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech. Dev. 101, 61–69.

    Article  PubMed  CAS  Google Scholar 

  72. Sauer, B. (1992) Identification of cryptic lox sites in the yeast genome by selection for Cre-mediated chromosome translocations that confer multiple drug resistance. J. Mol. Biol. 223, 911–928.

    Article  PubMed  CAS  Google Scholar 

  73. Lottmann, H., Vanselow, J., Hessabi, B., and Walther, R. (2001) The Tet-On system in transgenic mice: Inhibition of the mouse pdx-1 gene activity by antisense RNA expression in pancreatic beta-cells. J. Mol. Med. 79, 321–328.

    Article  PubMed  CAS  Google Scholar 

  74. Zhu, Z., Ma, B., Homer, R. J., Zheng, T., and Elias, J. A. (2001) Use of the tetra-cycline-controlled transcriptional silencer (tTS) to eliminate transgene leak in inducible overexpression transgenic mice. J. Biol. Chem. 276, 25222–25229.

    Article  PubMed  CAS  Google Scholar 

  75. Freundlieb, S., Schirra-Muller, C., and Bujard, H. (1999) A tetracycline controlled activation/repression system with increased potential for gene transfer into mammalian cells. J. Gene Med. 1, 4–12.

    Article  PubMed  CAS  Google Scholar 

  76. Wakita, K., McCormick, F., and Tetsu, O. (2001) Method for screening ecdysone-inducible stable cell lines. Biotechniques 31, 414–418.

    PubMed  CAS  Google Scholar 

  77. Saez, E., Nelson, M. C., Eshelman, B., Banayo, E., Koder, A., Cho, G. J., et al. (2000) Identification of ligands and coligands for the ecdysone-regulated gene switch. Proc. Natl. Acad. Sci. USA 97, 14512–14517.

    Article  PubMed  CAS  Google Scholar 

  78. Constantino, S., Santos, R., Gisselbrecht, S., and Gouilleux, F. (2001) The ecdysone inducible gene expression system: unexpected effects of muristerone A and ponasterone A on cytokine signaling in mammalian cells. Eur. Cytokine. Netw. 12, 365–367.

    PubMed  CAS  Google Scholar 

  79. Lee, C., Sensibar, J. A., Dudek, S. M., Hiipakka, R. A., and Liao, S. T. (1990) Prostatic ductal system in rats: regional variation in morphological and functional activities. Biol. Reprod. 43, 1079–1086.

    Article  PubMed  CAS  Google Scholar 

  80. Price, D. (1963) Comparative aspects of development and structure in the prostate, in Biology of the Prostate and Related Tissues (Vollmer, E. P. and Kauff-mann, G., eds.) US Government Printing Office, Washington, D.C., pp. 1–28.

    Google Scholar 

  81. Spence, A. M., Sheppard, P. C., Davie, J. R., Matuo, Y., Nishi, N., McKeehan, W. L., et al. (1989) Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin. Proc. Natl. Acad. Sci. USA. 86, 7843–7847.

    Article  PubMed  CAS  Google Scholar 

  82. Spence, A. M., Sheppard, P. C., Davie, J. R., Matuo, Y., Nishi, N., McKeehan, W. L., et al. (1989) Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin. Proc. Natl. Acad. Sci. USA 86, 7843–7847.

    Article  PubMed  CAS  Google Scholar 

  83. Matuo, Y., Nishi, N., Muguruma, Y., Yoshitake, Y., Kurata, N., and Wada, F. (1985) Localization of prostatic basic protein (“probasin”) in the rat prostates by use of monoclonal antibody. Biochem. Biophys. Res. Commun. 130, 293–300.

    Article  PubMed  CAS  Google Scholar 

  84. Dodd, J. G., Sheppard, P. C., and Matusik, R. J. (1983) Characterization and cloning of rat dorsal prostate mRNAs. Androgen regulation of two closely related abundant mRNAs. J. Biol. Chem. 258, 10731–10737.

    PubMed  CAS  Google Scholar 

  85. Rennie, P. S., Bruchovsky, N., Leco, K. J., Sheppard, P. C., McQueen, S. A., Cheng, H., et al. (1993) Characterization of two cis-acting elements involved in the androgen regulation of the probasin gene. Mol. Endocrinol. 7, 23–36.

    Article  PubMed  CAS  Google Scholar 

  86. Greenberg, N. M., DeMayo, F. J., Sheppard, P. C., Barrios, R., Lebovitz, M., Finegold, M., 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, 230–239.

    Article  PubMed  CAS  Google Scholar 

  87. Matusik, R. J., Kreis, C., McNicol, P., Sweetland, R., Mullin, C., Fleming, W. H., et al. (1986) Regulation of prostatic genes: role of androgens and zinc in gene expression. Biochem. Cell Biol. 64, 601–607.

    Article  PubMed  CAS  Google Scholar 

  88. Nachtigal, M. W., Nickel, B. E., Klassen, M. E., Zhang, W., Eberhardt, N. L., and Cattini, P. A. (1989) Human chorionic somatommammotropin and growth hormone gene expression in rat pituitary tumour cells is dependent on proximal promoter sequences. Nucleic Acids Res. 17, 4327–4337.

    Article  PubMed  CAS  Google Scholar 

  89. Zhang, J., Thomas, T. Z., Kasper, S., and Matusik, R. J. (2000) A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo. Endocrinology 141, 4698–4710.

    Article  PubMed  CAS  Google Scholar 

  90. Cleutjens, K. B., van der Korput, H. A., Ehren-van Eekelen, C. C., Sikes, R. A., Fasciana, C., Chung, L. W., et al. (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, 1256–1265.

    Article  PubMed  CAS  Google Scholar 

  91. Daelemans, D., De Clercq, E., and Vandamme, A. (2001) A quantitative GFP-based bioassay for the detection of HIV-1 Tat transactivation inhibitors. J. Virol. Methods 96, 183–188.

    Article  PubMed  CAS  Google Scholar 

  92. Veldscholte, J., Berrevoets, C. A., Ris-Stalpers, C., Kuiper, G. G., Jenster, G., Trapman, J., et al. (1992) The androgen receptor in LNCaP cells contains a mutation in the ligand binding domain which affects steroid binding characteristics and response to antiandrogens. J. Steroid Biochem. Mol. Biol. 41, 665–669.

    Article  PubMed  CAS  Google Scholar 

  93. Liu, N., Gao, F., Han, Z., Xu, X., Underhill, C. B., and Zhang, L. (2001) Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells. Cancer Res. 61, 5207–5214.

    PubMed  CAS  Google Scholar 

  94. Kasper, S., Rennie, P. S., Bruchovsky, N., Sheppard, P. C., Cheng, H., Lin, L., et al. (1994) Cooperative binding of androgen receptors to two DNA sequences is required for androgen induction of the probasin gene. J. Biol. Chem. 269, 31763–31769.

    PubMed  CAS  Google Scholar 

  95. Kasper, S., Rennie, P. S., Bruchovsky, N., Lin, L., Cheng, H., Snoek, R., et al. (1999) Selective activation of the probasin androgen responsive region by steroid hormones. J. Mol. Endocrinol. 22, 313–325.

    Article  PubMed  CAS  Google Scholar 

  96. Brookes, D. E., Zandvliet, D., Watt, F., Russell, P. J., and Molloy, P. L. (1998) Relative activity and specificity of promoters from prostate-expressed genes. Prostate 35, 18–26.

    Article  PubMed  CAS  Google Scholar 

  97. Yan, Y., Sheppard, P. C., Kasper, S., Lin, L., Hoare, S., Kapoor, A., et al. (1997) A large fragment of the probasin promoter targets high levels of transgene expression to the prostate of transgenic mice. Prostate 32, 129–139.

    Article  PubMed  CAS  Google Scholar 

  98. Sleigh, M. J., Topp, W. C., Hanich, R., and Sambrook, J. F. (1978) Mutants of SV40 with an altered small t protein are reduced in their ability to transform cells. Cell 14, 79–88.

    Article  PubMed  CAS  Google Scholar 

  99. Hogan, B., Beddington, R., Costantini, F., and Lacy, E. (eds.) (2001) Manipulating the Mouse Embryo, A Laboratory Manual, 2nd edition. Cold Springs Harbor Press.

    Google Scholar 

  100. Hayward, S. W., Brody, J. R., and Cunha, G. R. (1996) An edgewise look at basal epithelial cells: three-dimensional views of the rat prostate, mammary gland and salivary gland. Differentiation 60, 219–227.

    Article  PubMed  CAS  Google Scholar 

  101. Bonkhoff, H. and Remberger, K. (1998) Morphogenetic concepts of normal and abnormal growth in the human prostate. Virchows Arch. 433, 195–202.

    Article  PubMed  CAS  Google Scholar 

  102. Cox, M. E., Deeble, P. D., Bissonette, E. A., and Parsons, S. J. (2000) Activated 3′,5′-cyclic AMP-dependent protein kinase is sufficient to induce neuroendocrine-like differentiation of the LNCaP prostate tumor cell line. J. Biol. Chem. 275, 13812–13818.

    Article  PubMed  CAS  Google Scholar 

  103. Zelivianski, S., Verni, M., Moore, C., Kondrikov, D., Taylor, R., and Lin, M. F. (2001) Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype. Biochim. Biophys. Acta 1539, 28–43.

    Article  PubMed  CAS  Google Scholar 

  104. Gingrich, J. R., Barrios, R. J., Foster, B. A., and Greenberg, M. N. (1999) Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate Cancer Prostatic Dis. 6, 1–6.

    Google Scholar 

  105. Chaurand, P., DaGue, B. B., Ma, S., Kasper, S., and Caprioli, R. M. (2001) Strainbased sequence variations and structure analysis of murine prostate specific spermine binding protein using mass spectrometry. Biochemistry 40, 9725–9733.

    Article  PubMed  CAS  Google Scholar 

  106. Zhang Z. F., Thomas, T. Z., Kasper, S., and Matusik, R. J. (2000) A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoid in vitro and in vivo. Endocrinology 141, 4698–4710.

    Article  PubMed  CAS  Google Scholar 

  107. Andriani, F., Nan, B., Yu, J., Li, X., Weigel, N. L., McPhaul, et al. (2001) Use of the probasin promoter arr(2)pb to express bax in androgen receptor-positive prostate cancer cells. J. Natl. Cancer Inst. 93, 1314–1324.

    Article  PubMed  CAS  Google Scholar 

  108. Chaurand, P., Stoeckli, M., and Caprioli, R. M. (1999) Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal. Chem. 71, 5263–5270.

    Article  PubMed  CAS  Google Scholar 

  109. Hamer, D.H. and Walling, M. (1982) Regulation in vivo of a cloned mammalian gene: cadmium induces the transcription of a mouse metallothionein gene in SV40 vectors. J. Mol. Appl. Genet. 1, 273–288.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN

    Susan Kasper & William Tu

  2. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN

    William Tu

  3. Department of Pathology and The Vanderbilt Prostate Cancer Center, Vanderbilt University Medical Center, Nashville, TN

    Richard L. Roberts

  4. The Vanderbilt Prostate Cancer Center, Departments of Urologic Surgery and Pathology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN

    Scott B. Shappell

Authors
  1. Susan Kasper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Tu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard L. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott B. Shappell
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Oncology Research Centre, Prince of Wales Hospital, Randwick, Australia

    Pamela J. Russell , Paul Jackson  & Elizabeth A. Kingsley ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc.

About this protocol

Cite this protocol

Kasper, S., Tu, W., Roberts, R.L., Shappell, S.B. (2003). Transgenic Mouse Models for Prostate Cancer. In: Russell, P.J., Jackson, P., Kingsley, E.A. (eds) Prostate Cancer Methods and Protocols. Methods in Molecular Medicine™, vol 81. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-372-0:113

Download citation

  • DOI: https://doi.org/10.1385/1-59259-372-0:113

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-0-89603-978-0

  • Online ISBN: 978-1-59259-372-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation