ANDROGEN UP-REGULATES EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION ANDBINDING-AFFINITY IN PC3 CELL-LINES EXPRESSING THE HUMAN ANDROGEN RECEPTOR

Androgens are required for the optimal growth and development of both the normal prostate and steroid-sensitive prostate cancer. PC3 prostat e cancer cell lines stably expressing the human androgen receptor (AR) and possessing an androgen-sensitive phenotype (PC3-hAR) were used to examine the role of the epidermal growth factor receptor (EGFR) in an drogen-stimulated prostate cancer cell growth. Epidermal growth factor (EGF) and dihydrotestosterone (DHT) independently induced the growth of PC3-hAR cells. Moreover, EGF and DHT in combination exerted a syner gistic effect on PC3-hAR cell growth. DHT-exposed PC3-hAR cells expres sed a greater than 2-fold increase in EGFR mRNA and 50% more EGFR prot ein than controls. Time course radioligand-binding assays confirmed th ese findings by showing an elevation in EGF binding in the DHT-esposed PC3-hAR cells. In addition, radioligand competition-binding studies r evealed a 2-fold increase in EGFR-EGF binding affinity in the PC3-hAR cells after DHT treatment. However, no enhancement of transforming gro wth factor alpha or EGF expression was detected because DHT did not af fect the levels of these cytokines in the PC3-hAR cell lysate or condi tioned media. Our observations suggest that DHT increases both EGFR nu mber and receptor-ligand affinity in androgen-sensitive prostate cance r cells and that these effects correlate with increased EGF binding an d an enhanced mitogenic response to EGF.