Inhibition of growth and cell cycle arrest of ARCaP human prostate cancer cells by ectopic expression of ER-alpha.

The estrogen receptor-alpha (ER-alpha) is a ligand-dependent transcription factor that regulates the growth, differentiation, and development of hormone-responsive target organs. While ER-alpha has been reported to play critical role in the pathogenesis and prognosis of breast and prostate cancers, its possible functional role in regulating prostate cancer cell growth in a ligand-dependent or -independent manner is poorly understood. We addressed this question by stably transfecting wild type (wt) ER-alpha cDNA into an invasive estrogen receptor-negative human prostate cancer cell line ARCaP. We isolated several clonal lines of transfected cells expressing varying levels of ER-alpha. The ectopic expression of wt ER-a markedly inhibited the growth of ARCaP cells in vitro in an ER-a dose-dependent but ligand-independent manner. Flow cytometric analysis of the wt ER-alpha-transfected ARCaP cells revealed that wt ER-alpha expression arrested cell growth in G1 phase. Our results suggest that ER-alpha may regulate prostate cell growth and participate in the pathogenesis of prostate cancer. ER-alpha may be delivered and expressed ectopically to target prostate cancer progression.