This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Asamoto, M. Articles by Shirai, T. Search for Related Content PubMed PubMed Citation Articles by Asamoto, M. Articles by Shirai, T.

Prostate Carcinomas Developing in Transgenic Rats with SV40 T Antigen Expression under Probasin Promoter Control Are Strictly Androgen Dependent¹

First Department of Pathology, Nagoya City University Medical School, Nagoya 467-8601, Japan

We have generated a transgenic rat with the SV40 T antigen under probasin promoter control, allowing prostate-specific gene expression. Males demonstrate atypical epithelial cell proliferation in the prostate from 4 weeks of age and develop prostate carcinomas at 100% incidence before they are 15 weeks old. Castration at 5 weeks of age was found to inhibit the prostate tumor formation completely, whereas testosterone propionate administration induced marked cell proliferation as well as microinvasion in prostate carcinomas. Castration at 20 weeks of age, after tumor development, even with testosterone propionate treatment, induced complete tumor involution within 5 weeks. To investigate the underling processes, sequential histological changes were monitored 1, 2, 3, 7, 14, and 21 days after castration. At days 1–3, many apoptotic bodies and inflammatory cells, including foam cells, were observed, and clear glandular structures were no longer evident in the tumors. Seven days after castration, most glands were involved, and nuclei of the cells did not show atypia. After 14 and 21 days, only atrophic glands were observed. During this process, expression of caspase 3, caspase 6, BAX, bcl-x, TRPM-2, and MMP7 genes was apparently increased. Comparison of the gene expression profile between a prostate carcinoma in a transgenic animal and a normal prostate of a wild-type rat by a cDNA array technique was also conducted. The results suggested that our model is suitable to investigate mechanisms of carcinogenesis, including androgen dependence, involution, and apoptosis.

This article has been cited by other articles:

				N. Hokaiwado, F. Takeshita, A. Naiki-Ito, M. Asamoto, T. Ochiya, and T. Shirai Glutathione S-transferase Pi mediates proliferation of androgen-independent prostate cancer cells Carcinogenesis, June 1, 2008; 29(6): 1134 - 1138. [Abstract] [Full Text] [PDF]

				Z. Wang, R. M. Luque, R. D. Kineman, V. H. Ray, K. T. Christov, D. D. Lantvit, T. Shirai, S. Hedayat, T. G. Unterman, M. C. Bosland, et al. Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat Endocrinology, March 1, 2008; 149(3): 1366 - 1376. [Abstract] [Full Text] [PDF]

				S. Yamashita, K. Wakazono, T. Nomoto, Y. Tsujino, T. Kuramoto, and T. Ushijima Expression Quantitative Trait Loci Analysis of 13 Genes in the Rat Prostate Genetics, November 1, 2005; 171(3): 1231 - 1238. [Abstract] [Full Text] [PDF]

				N. Hokaiwado, M. Asamoto, K. Ogawa, and T. Shirai Transgenic Disruption of Gap Junctional Intercellular Communication Enhances Early but Not Late Stage Hepatocarcinogenesis in the Rat Toxicol Pathol, October 1, 2005; 33(6): 695 - 701. [Abstract] [Full Text] [PDF]

				Y. Zeng, M. Yokohira, K. Saoo, H. Takeuchi, Y. Chen, K. Yamakawa, Y. Matsuda, Y. Kakehi, and K. Imaida Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor Carcinogenesis, June 1, 2005; 26(6): 1109 - 1116. [Abstract] [Full Text] [PDF]

				A. Omezzine, C. Mauduit, E. Tabone, N. Nabli, A. Bouslama, and M. Benahmed Caspase-3 and -6 Expression and Activation Are Targeted by Hormone Action in the Rat Ventral Prostate During the Apoptotic Cell Death Process Biol Reprod, September 1, 2003; 69(3): 752 - 760. [Abstract] [Full Text] [PDF]

				M. Grzmil, P. Thelen, B. Hemmerlein, S. Schweyer, S. Voigt, D. Mury, and P. Burfeind Bax Inhibitor-1 Is Overexpressed in Prostate Cancer and Its Specific Down-Regulation by RNA Interference Leads to Cell Death in Human Prostate Carcinoma Cells Am. J. Pathol., August 1, 2003; 163(2): 543 - 552. [Abstract] [Full Text] [PDF]

				C. J. Thompson, N. N. C. Tam, J. M. Joyce, I. Leav, and S.-m. Ho Gene Expression Profiling of Testosterone and Estradiol-17{beta}-Induced Prostatic Dysplasia in Noble Rats and Response to the Antiestrogen ICI 182,780 Endocrinology, June 1, 2002; 143(6): 2093 - 2105. [Abstract] [Full Text] [PDF]

				G. O. Hellawell, G. D. H. Turner, D. R. Davies, R. Poulsom, S. F. Brewster, and V. M. Macaulay Expression of the Type 1 Insulin-like Growth Factor Receptor Is Up-Regulated in Primary Prostate Cancer and Commonly Persists in Metastatic Disease Cancer Res., May 1, 2002; 62(10): 2942 - 2950. [Abstract] [Full Text] [PDF]

				M. Asamoto, N. Hokaiwado, Y.-M. Cho, and T. Shirai Effects of genetic background on prostate and taste bud carcinogenesis due to SV40 T antigen expression under probasin gene promoter control Carcinogenesis, March 1, 2002; 23(3): 463 - 467. [Abstract] [Full Text] [PDF]