Characterization of soy-based changes in Wnt-frizzled signaling in prostate cancer.
BACKGROUND
A soy-based diet has been associated with a decreased risk of prostate cancer through its anti-androgenic effects. Because the Wnt/beta catenin pathway has been associated with aggressive prostate cancer, we have sought to further evaluate this pathway with respect to soy protein and prostate cancer.


METHODS
Previously we have treated rat and human prostate cancer cell lines with soy protein isolates or purified genistein and used gene expression profiling and cross species analysis to identify genes with similar expression changes. One pathway that was identified included the Wnt/beta-cantenin pathway. Here the initial data are evaluated and extended with immunohistochemistry in human prostate cancer, and Western blotting, small interfering ribonucleic acid (siRNA) inhibition and bromodeoxyuridine (BrDU) labeling in prostate cancer cell lines.


RESULTS
The Wnt/beta-catenin pathway is modulated by both soy protein isolates and genistein in the genomic results. Immunohistochemistry demonstrated staining of Wnt pathway component molecules, in particular frizzled 3, glycogen synthase kinase 3 (GSK-3), and beta-catenin, in prostate tumors. Western blotting noted increased GSK3 and decreased expression of beta-catenin in soy treated prostate cancer PC3 cells. Supporting this finding, siRNA blocking of GSK3 accelerated growth whereas inhibition of frizzled 3 suppressed growth based on growth curves and BrDU labeling.


CONCLUSIONS
Soy protein appears to regulate prostate cancer via the Wnt/beta-catenin pathway. These data demonstrate that the effect of soy protein effect on prostate cancer may occur through the frizzled 3 receptor with activation of GSK3 leading to increased degradation of beta-catenin and cell growth.
Liss
Michael A
MA
Department of Urology, University of California-Irvine, Irvine, CA, U.S.A. mliss@uci.edu
Schlicht
Michael
M
Kahler
Andrea
A
Fitzgerald
Ryan
R
Thomassi
Taylor
T
Degueme
Amy
A
Hessner
Martin
M
Datta
Milton W
MW
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D051157:Frizzled Receptors / Q000378:metabolism*; D020869:Gene Expression Profiling; D019833:Genistein / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D030262:Soybean Proteins / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
C105574:FZD3 protein, human; D051157:Frizzled Receptors; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D030262:Soybean Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D019833:Genistein; D038362:Glycogen Synthase Kinase 3; D001973:Bromodeoxyuridine