Ilma Simoni Brum da Silva

ANDROGEN-INDUCED CELL GROWTH AND C-MYC EXPRESSION IN HUMAN NON-TRANSFORMED EPITHELIAL PROSTATIC CELLS IN PRIMARY CULTURE

We assessed androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic (HNTEP) cells in primary culture. Prostatic tissue was obtained from 48 retropubic prostatectomy patients (age: 61–77 years) with benign prostatic hyperplasia (malignant tumors excluded). HNTEP cells were treated with testosterone or DHT, alone or in association with hydroxyflutamide. DHT action on c-myc mRNA was examined using Northern blots and RT-PCR. RT-PCR also was used to verify if HNTEP cells expressed the androgen receptor gene. Cell proliferation was assessed on days 3 and 6. Testosterone (2 × 10−11 M) and DHT (10−13 M) caused a significant increase (P < 0.05) in cell proliferation on both days. Addition of hydroxyflutamide (10−6 M) to DHT abolished cell proliferation. HNTEP cells expressed androgen receptor (AR) gene and the treatment with DHT increased AR mRNA levels. C-myc expression was maximal at 30 min and 1 h with DHT (10−13 M). C-myc seems to play a key role in the control of hormone responsiveness and cell proliferation in epithelial prostatic cells. The detection of androgen receptor gene expression and the increase in this expression with the addition of androgen shows that the HTNEP cells maintain functional characteristics and hormone dependence, and that they are a fruitful in vitro model for studying steroid hormone action mechanisms.