The effects of dihydrotestosterone on the expression of p185(erbB-2) and c-erbB-2 mRNA 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 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.
Myers
R B
RB
Department of Pathology, The University of Alabama at Birmingham, USA.
Oelschlager
D K
DK
Hockett
R D
RD
Rogers
M D
MD
Conway-Myers
B A
BA
Grizzle
W E
WE
D013196:Dihydrotestosterone / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D013196:Dihydrotestosterone; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D013936:Thymidine; D014316:Tritium; C000715470:MAS1 protein, human