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 res ponsive MCF-7 human breast cancer cells. We now demonstrate that andro gen withdrawal leads to a significant stimulation of TGF beta-2 mRNA i n the androgen-responsive human prostate carcinoma cell line LNCaP. Th ese data indicate that TGF beta-2 is a marker of (anti)androgen action in human prostate cancer in vitro. Based on these results we addresse d the question of whether TGF beta-2 represented a marker of (anti)and rogen action in prostate cancer in vivo : expression of TGF beta mRNA was determined by RNAase protection analysis in normal and malignant p rostate tissue obtained from 9 prostate carcinoma patients without end ocrine therapy. In parallel, the nuclear dihydrotestosterone (DHT) con centration was measured as an indicator of androgen stimulation in the same tissues. The following results were obtained. Both normal and ca ncerous tissues show nuclear accumulation of DHT indicating a function al androgen receptor system. TGF beta-2 is equally expressed in both n ormal and cancerous tissue. Expression of TGF beta-2 and nuclear DHT c oncentrations are correlated in both benign and malignant tissue. We c onclude that TGF beta-2 is a marker of(anti)hormonal action in androge n-dependent tissue.