Document Detail


Characterization of soy-based changes in Wnt-frizzled signaling in prostate cancer.
MedLine Citation:
PMID:  20952759     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
MATERIALS AND 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.
CONCLUSION: 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.
Authors:
Michael A Liss; Michael Schlicht; Andrea Kahler; Ryan Fitzgerald; Taylor Thomassi; Amy Degueme; Martin Hessner; Milton W Datta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer genomics & proteomics     Volume:  7     ISSN:  1790-6245     ISO Abbreviation:  Cancer Genomics Proteomics     Publication Date:    2010 Sep-Oct
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-01-31     Revised Date:  2012-01-18    
Medline Journal Info:
Nlm Unique ID:  101188791     Medline TA:  Cancer Genomics Proteomics     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  245-52     Citation Subset:  IM    
Affiliation:
Department of Urology, University of California-Irvine, Irvine, CA, U.S.A. mliss@uci.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Bromodeoxyuridine
Cell Line, Tumor
Frizzled Receptors / metabolism*
Gene Expression Profiling
Genistein / pharmacology*
Glycogen Synthase Kinase 3 / metabolism
Humans
Male
Prostatic Neoplasms / metabolism*
RNA, Small Interfering
Rats
Receptors, G-Protein-Coupled / metabolism
Signal Transduction / drug effects*
Soybean Proteins / pharmacology*
Wnt Proteins / metabolism*
beta Catenin / metabolism
Grant Support
ID/Acronym/Agency:
R25CA059756/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/FZD3 protein, human; 0/Frizzled Receptors; 0/RNA, Small Interfering; 0/Receptors, G-Protein-Coupled; 0/Soybean Proteins; 0/Wnt Proteins; 0/beta Catenin; 446-72-0/Genistein; 59-14-3/Bromodeoxyuridine; EC 2.7.11.26/Glycogen Synthase Kinase 3
Comments/Corrections
Erratum In:
Cancer Genomics Proteomics. 2011 Mar-Apr;8(2):103

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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