HORMONAL-REGULATION OF TRANSFORMING GROWTH-FACTOR-BETA-2 EXPRESSION IN HUMAN PROSTATE-CANCER

We have previously shown that a transforming factor-beta species (TGF beta) is a hormonally regulated negative growth factor in estrogen responsive MCF-7 human breast cancer cells. We now demonstrate that androgen withdrawal leads to a significant stimulation of TGF beta-2 mRNA in the androgen-responsive human prostate carcinoma cell line LNCaP. These data indicate that TGF beta-2 is a marker of (anti)androgen action in human prostate cancer in vitro. Based on these results we addressed the question of whether TGF beta-2 represented a marker of (anti)androgen action in prostate cancer in vivo : expression of TGF beta mRNA was determined by RNAase protection analysis in normal and malignant prostate tissue obtained from 9 prostate carcinoma patients without endocrine therapy. In parallel, the nuclear dihydrotestosterone (DHT) concentration was measured as an indicator of androgen stimulation in the same tissues. The following results were obtained. Both normal and cancerous tissues show nuclear accumulation of DHT indicating a functional androgen receptor system. TGF beta-2 is equally expressed in both normal and cancerous tissue. Expression of TGF beta-2 and nuclear DHT concentrations are correlated in both benign and malignant tissue. We conclude that TGF beta-2 is a marker of(anti)hormonal action in androgen-dependent tissue.