Cancer Genomics & Proteomics, 2010, 7(5):245-52.

Characterization of soy-based changes in Wnt-frizzled signaling in prostate cancer

MICHAEL A. LISS, MARTIN HESSNER, et al

Department of Urology, University of California Irvine, Irvine, CA, U.S.A.; Department of Pathology, University of Minnesota, Minneapolis, MN, U.S.A.; et al

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. 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. 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. 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.

希腊《肿瘤基因组学和蛋白质组学》，2010年

前列腺癌中Wnt-frizzled信号基于大豆的变化特征

迈克尔 A 利斯，马丁 · 赫斯纳

美国加利福尼亚大学欧文分校泌尿外科，美国明尼苏达大学病理学系等

由于抗雄性激素作用，大豆基饮食与患前列腺癌风险降低有关。因为 Wnt/β 连环蛋白通路与侵略性前列腺癌有关，我们试图进一步评价这一途径与大豆蛋白和前列腺癌的关系。以前我们用大豆蛋白分离物或纯化的金雀异黄素来治疗大鼠和人类的前列腺癌细胞株，并且使用基因表达谱图和跨物种分析来识别基因相似表达的变化。一种被识别的途径包括 Wnt/β-连环蛋白通路。这里，用免疫组织化学法来评价和扩展前列腺癌细胞株中的初始数据，并且对免疫印迹、 小干扰核糖核酸 (siRNA) 抑制和溴脱氧尿甙 (BrDU)进行标记。在基因组结果中，Wnt/β-连环蛋白通路被大豆分离蛋白和染料木黄酮调节。免疫组织化学染色解释了前列腺肿瘤参与Wnt 途径的分子，特别是frizzled 3，糖原合酶激酶 3 (GSK-3)，和 β-连环蛋白。免疫印迹法强调用大豆治疗的前列腺癌 PC3 细胞GSK3有所增加，而 β-连环蛋白表达降低。siRNA 阻断了 GSK3的 加速增长，而基于生长曲线和 BrDU 标记frizzled- 3 抑制生长支持这一发现。大豆蛋白似乎可以通过 Wnt/β-连环蛋白通路调节前列腺癌。这些数据表明，大豆蛋白对前列腺癌的作用，可能通过frizzled 3 受体活化GSK3 引起的β-连环蛋白和细胞生长的大幅度退化实现。