Regulation of androgen receptor by androgen and epidermal growth factor in a human prostatic cancer cell line, LNCaP.
The effects of androgen and epidermal growth factor (EGF) on cell proliferation and the expression of mRNA and protein of androgen receptor (AR) were examined in an androgen-sensitive human prostatic cancer cell line, LNCaP, by Northern and Western blot analyses. The addition of 1 nM dihydrotestosterone (DHT), at which the proliferation of the cells was most stimulated, did not change the level of AR mRNA but increased the level of AR protein by reducing the turnover rate of the AR protein. EGF also stimulated the proliferation of the cells but repressed the expression of AR mRNA and protein. This repression was found to be exerted primarily at the level of transcription. When DHT and EGF were added simultaneously to the cells, the level of AR mRNA was reduced to the same degree as was accomplished by the addition of EGF alone. On the other hand, the level of AR protein increased but this increase was about 70% of that attained following the addition of DHT alone. The stimulatory effects of EGF and DHT on cell proliferation were found to be additive. These results indicate that EGF down-regulates the level of AR mRNA and thereby also that of AR protein irrespective of the presence of DHT, and that EGF stimulates the proliferation of LNCaP cells through a different pathway from that of DHT.
Mizokami
A
A
Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Saiga
H
H
Matsui
T
T
Mita
T
T
Sugita
A
A
D000728:Androgens / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D004815:Epidermal Growth Factor