Suppressive effects of antiandrogens, finasteride and flutamide on development of prostatic lesions in a transgenic rat model.
Transgenic (TG) rats bearing a probasin promoter/simian virus 40 T antigen (SV40 Tag) construct were treated with antiandrogens to examine their ability to suppress prostate carcinogenesis. Finasteride and flutamide were administered to 10-week-old TG rats five times a week for 2, 5 and 7 weeks. Antiandrogen-treated prostates exhibited atrophic glandular structures with almost no expression of SV40 Tag and only weak signals for androgen receptors. Furthermore, quantitative data for ventral prostate adenocarcinomas showed significant decrease with antiandrogen treatment. Both finasteride and flutamide had the ability to suppress SV40 Tag-driven carcinogenesis through their different antiandrogenic mechanisms, suggesting that this TG model is suitable for exploring the potential of agents to inhibit prostate cancer development.
Cho
Y-M
YM
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
Takahashi
S
S
Asamoto
M
M
Suzuki
S
S
Tang
M
M
Shirai
T
T
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D000957:Antigens, Viral, Tumor / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018120:Finasteride / Q000627:therapeutic use*; D005485:Flutamide / Q000627:therapeutic use*; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D000957:Antigens, Viral, Tumor; D004791:Enzyme Inhibitors; D013739:Testosterone; D018120:Finasteride; D005485:Flutamide