The effects of dihydrotestosterone on the expression of p185(erbB-2) and c-erbB-2 mRNA in the prostatic cell line LNCaP.

Academic Article

Abstract

  • The c-erbB-2 proto-oncogene encodes a 185000 molecular weight protein (p185(erbB-2)) which shares structural homology with the epidermal growth factor (EGF) receptor. We examined the effects of dihydrotestosterone (DHT) on the expression of p185(erbB2) and c-erbB-2 mRNA in the human 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 immunoprecipitation of 35S-methionine labelled p185(erbB-2). c-erbB-2 mRNA levels were determined using a competitive quantitative reverse transcription-polymerase chain reaction (RT-PCR) based technique. DHT at concentrations of 10(-9) M or greater resulted in decreased expression of p185(erbB-2). In contrast, DHT at these levels stimulated EGF receptor protein expression and cellular proliferation. c-erbB-2 mRNA levels declined to 30-50% of control levels following treatment with DHT of 10(-10) M or greater. Furthermore, the inhibitory effects on c-erbB-2 mRNA were rapid, occurring within 6-12 h of treatment. In summary, these results demonstrate that DHT, at concentrations that stimulate cell growth, inhibits the expression of p185(erbB-2) and c-erbB-2 mRNA.
  • Keywords

  • Dihydrotestosterone, Gene Expression Regulation, Neoplastic, Humans, Male, Prostatic Neoplasms, RNA, Messenger, Receptor, ErbB-2, Thymidine, Tritium, Tumor Cells, Cultured
  • Author List

  • Myers RB; Oelschlager DK; Hockett RD; Rogers MD; Conway-Myers BA; Grizzle WE
  • Start Page

  • 441
  • End Page

  • 447
  • Volume

  • 59
  • Issue

  • 5-6