Role of the TGF-Beta 1 in the Prevention of Prostate Cancer
Abstract
Our preliminary data showed that antiandrogen (toremifene) and antiestrogen (flutamide) prevented cancer in the TRAMP transgenic model. We hypothesized that these agents inhibit prostate carcinogenesis through stimulation of TGFB production. This hypothesis is being tested through two specific aims: 1) whether the chemopreventive biologic effects of antiandrogens, antiestrogens and retinoic acid are mediated by TGFB in the TRAMP model, 2) whether prostate cancer may be prevented in the TRAMP model at the genetic level by crossbreeding with transgenic mice engineered to overexpress TGFB. While the retinoid MD1301 was ineffective, both flutamide and toremifene were able to delay onset of prostate cancer. The mechanism of this suppression may be different for the two agents: flutamide inhibited but toremifene did not affect large T-antigen expression. Toremifene treated animals had higher total and free testosterone levels. However, androgen receptor levels were similar for placebo and toremifene treated animals. Since toremifene inhibited prostate cancer in a milieu of elevated free testosterone levels the mechanism of toremifene chemopreventive activity appears to be through nonandrogenic pathways. One potential mechanism may be through stimulation of TOFB. TGFB overexpression in the prostate or seminal vesicles delayed tumor development in the TRAMP mice through autocrine and paracrine pathways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2001
- Accession Number
- ADA392511
Entities
People
- Mitchell Steiner
Organizations
- University of Tennessee