Involvement of the estrogen receptor beta in genistein-induced expression of p21(waf1/cip1) in PC-3 prostate cancer cells.
BACKGROUND
Dietary genistein, a phytoestrogen derived from soybean, has been suggested as a chemopreventive agent for prostate cancer. Genistein has been reported to exert its anticancer effects via a variety of functional pathways, but the upstream signaling of molecules regulated by genistein remains unclear. In this study, estrogen receptor (ER) beta involvement in genistein-induced expression of cell cycle inhibitors in PC-3 prostate cancer cells was investigated.


METHODS
The proliferation of PC-3 cells exposed to genistein was measured by the water-soluble tetrazolium salt (WST-1) proliferation assay. The expression of p21, p27 and ERbeta in the PC-3 cells was assessed by quantitative real-time reverse transcription-PCR. ERbeta silencing was performed using a small interfering RNA (siRNA). The transcriptional activity of the p21 promoter was determined by the luciferase reporter assay.


RESULTS
Genistein caused marked inhibition of proliferative activity and induced the expression of p21 and ERbeta in the PC-3 cells. The siRNA against ERbeta suppressed the genistein-induced expression of p21 and reduced the transactivation activity of the p21 promoter induced by genistein.


CONCLUSIONS
ERbeta is involved in genistein-induced expression of p21 in PC-3 cells.
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Kentaro
K
Matsumura
Tomoaki
T
Tanaka
Hidenori
H
Kawashima
Tatsuya
T
Nakatani
D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000502:physiology*; D015870:Gene Expression; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047629:Estrogen Receptor beta; D034741:RNA, Small Interfering; D019833:Genistein