Expression of sex steroid receptor genes and comodulation with retinoid signaling in normal human uroepithelial cells and bladder cancer cell lines.

ABSTRACT

The expression of sex steroid receptor genes in human uroepithelial cells (UEC) and their role in bladder carcinogenesis is unknown. Expression of androgen receptor (hAR), estrogen receptor (hER), and vitamin d3 receptor (hVDR3) genes in normal human stromal cells (SC) and UEC, six bladder cancer cell lines, and two SV-40-immortalized cell lines (SVC) was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Functionality was assessed indirectly by relative RT-PCR, which identified comodulation of mRNA expression between retinoic acid and sex steroid receptor genes. UEC and SC expressed hAR and hER mRNA constitutively at low levels, but only positive controls expressed hVDR3. Every cancer cell line and the SVC showed aberrant expression. Treatment of cells with all-trans-retinoic acid up-regulated hAR and hER expression, whereas treatment with sex steroids up-regulated retinoic acid receptor expression. Cell proliferation was not affected by sex steroids or by their inhibitors. Sex steroid signaling pathways are functional in UEC and appear to be altered during bladder tumorigenesis. The sex steroid receptors may play a role in normal differentiation.