Al. Brass et al., ANDROGEN UP-REGULATES EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION ANDBINDING-AFFINITY IN PC3 CELL-LINES EXPRESSING THE HUMAN ANDROGEN RECEPTOR, Cancer research, 55(14), 1995, pp. 3197-3203
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.