THE EFFECTS OF DIHYDROTESTOSTERONE ON THE EXPRESSION OF P185(ERBB-2) AND C-ERBB-2 MESSENGER-RNA IN THE PROSTATIC CELL-LINE LNCAP

The c-erbB-2 proto-oncogene encodes a 185000 molecular weight protein (p185(erbB-2)) which shares structural homology with the epidermal gro wth factor (EGF) receptor. We examined the effects of dihydrotestoster one (DHT) on the expression of p185(erbB-2) and c-erbB-2 mRNA in the h uman malignant prostatic cell line LNCaP. LNCaP cells grown in steroid -depleted media were treated with DHT (10(-11)-10(-6) M) for 48 h and p185(erbB-2) expression was determined by Western blotting and immunop recipitation of S-35-methionine labelled p185(erbB-2) c-erbB-2 mRNA le vels were determined using a competitive quantitative reverse transcri ption-polymerase chain reaction (RT-PCR) based technique. DHT at conce ntrations of 10(-9) M or greater resulted in decreased expression of p 185(erbB-2). In contrast, DHT at these levels stimulated EGF receptor protein expression and cellular proliferation. c-erbB-2 mRNA levels de clined to 30-50% of control levels following treatment with DHT of 10( -10) M or greater. Furthermore, the inhibitory effects on c-erbB-2 mRN A were rapid, occurring within 6-12 h of treatment. In summary, these results demonstrate that DHT, at concentrations that stimulate cell gr owth, inhibits the expression of p185(erbB-2) and c-erbB-2 mRNA. Copyr ight (C) 1996 Elsevier Science Ltd.