Signal‐transduction pathways in androgen‐dependent and androgen‐independent prostate tumor cells

Abstract

AbstractWe have investigated the differential responses of androgen‐dependent prostate tumor cell line LNCaP and androgen‐independent prostate tumor cell line PC‐3 to various effectors at the level of mitogen‐activated protein kinase (MAPK) signal‐transduction intermediates. We have examined the change in protein levels of ras, raf, mek1,2, and erk1,2 in LNCaP and PC‐3 cells following treatment with dihydrotestosterone (DHT), estradiol (E2), ionizing radiation, tumor necrosis factor alpha (TNFα), ZnSO4, and CdSO4, DHT treatment of androgen‐dependent LNCaP cells resulted in an increase in cellular ras protein levels by 1 hour after treatment, whereas ras levels decreased 0.5 hours after DHT treatment of androgen‐independent PC‐3 cells. These data indicate that, in fact, DHT does invoke a differential response in androgen‐dependent compared to androgenindependent prostate tumor cells. E2 treatment resulted in a change in ras levels for LNCaP cells, but not for PC‐3 cells, which is further evidence of a differential response in these prostate tumor cells. Ionizing radiation, TNFα, and CdSO4 treatment showed no effect on signal‐transduction intermediates; however, ZnSO4 treatment of LNCaP cells resulted in an increase in ras protein levels and a decrease in raf‐1 protein levels. No change in ras levels was observed in PC‐3 cells upon ZnSO4 treatment. Our data show few differences in the signal‐transduction intermediates of the MAPK pathway in LNCaP and PC‐3 prostate tumor cells in response to tested stimuli. These results and the observation that cellular mek1,2 and erk1,2 protein levels were constituitively elevated support the hypothesis that MAPK‐independent signal transduction may be occurring in these prostate cells. © 1995 Wiley‐Liss, Inc.