Cyclin D1 (CCND1) expression is involved in estrogen receptor beta (ERβ) in human prostate cancer

BACKGROUND Estrogen receptor beta (ERβ) has been demonstrated to be expressed in prostate carcinoma cells and estrogen signals through ERβ to act as a tumor suppressor in prostate cancer patients. ERβ is thought to regulate the cell cycle of prostate carcinoma cells by controlling the expression of cell cycle regulators including cyclin D1 (CCND1). This interaction is of particular interest as CCND1 has been implicated in the development of prostate cancer. METHODS We evaluated ERβ and CCND1 immunoreactivity in human prostate cancer (n = 112, surgical specimens), and correlated the findings with clinicopathological features of the patients. Subsequent in vitro experiments using PC-3 prostate carcinoma cells were also performed to examine whether estradiol (E₂) could change the expression level of CCND1 mRNA. RESULTS CCND1 immunoreactivity was detected in 78/112 cases (70%), and was significantly correlated with incidence of perineural invasion and ERβ immunoreactivity (P < 0.05). Forty-eight hours incubation with E₂ (10 nM) increased the expression level of CCND1 mRNA as well as c-jun (JUN) and c-fos (FOS) in PC-3 cells, and PHTPP (ERβ antagonist) suppressed E₂-induced expression of those mRNAs. CONCLUSIONS These findings suggest that CCND1 expression is possibly regulated by estrogens via ERβ and that this signaling pathway may influence prostate cancer development. Prostate 73: 590-595, 2013. © 2012 Wiley Periodicals, Inc.