Androgen-modulated p21 and p53 gene expression in human non-transformed epithelial prostatic cells in primary cultures

摘要

The prostate gland is under androgen control. The aim of the present study was to evaluate the expression of two genes that are regulators of the cell cycle, the p53 and p21 genes, in human non-transformed epithelial prostatic cells (HNTEPs) treated with different concentrations of hormones. Samples of prostate tissue were obtained from 10 patients between 60 and 77 years of age. HNTEP cells were grown in basal medium and treated with dihydrotestosterone (DHT) in different conditions for 4?h. A low concentration of DHT resulted in a significant increase in cell growth; this effect was eradicated by addition of the antiandrogen hydroxyflutamide. Furthermore, the low concentration of DHT induced lower mRNA levels in the p53 and p21 genes in HNTEP cells. In turn, high DHT concentrations induced a significant increase in the expression of the p53 and p21 genes. The present data suggest that the p53 and p21 genes play a role in the control of responsiveness and androgen dose-dependent cell proliferation in HNTEP cells. Further studies are required to assess the intracellular signaling pathway regulated by p53 and p21 under the influence of androgens and its implications for the pathophysiology of prostate diseases.