Genistein affects androgen-responsive genes through both androgen- and estrogen-induced signaling pathways.
This study examined the mechanisms by which the prostate cancer chemopreventive agent genistein modulates gene expression in LNCaP human prostate cancer cells. Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells cultured in the presence or absence of hormonal stimulation and the presence or absence of genistein. Genistein strongly suppressed basal expression of androgen-responsive gene (ARG) mRNAs, including prostate-specific antigen (PSA) and Ste20-related proline-alanine-rich kinase (SPAK). However, genistein had little or no effect on basal expression of two other ARGs, beta2-microglobulin (B2M) or selenoprotein P (SEPP1). Culturing LNCaP cells in the presence of the synthetic androgen R1881-induced increases in PSA, SPAK, B2M, and SEPP1 mRNA levels. The R1881-induced expression of these genes was uniformly blocked by genistein. For PSA and SPAK, genistein also blocked or downregulated 17beta-estradiol-induced increases in mRNA expression. These results indicate that genistein selectively alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen- and estrogen-induced signaling pathways.
Takahashi
Yoko
Y
Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, Maryland 20705, USA.
Hursting
Stephen D
SD
Perkins
Susan N
SN
Wang
Tien-Chung
TC
Wang
Thomas T Y
TT
D000728:Androgens / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004967:Estrogens / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015741:Metribolone / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*
D000728:Androgens; D004967:Estrogens; D012333:RNA, Messenger; D015741:Metribolone; D019833:Genistein; D017430:Prostate-Specific Antigen