Overexpression of HER-2/neu enhances the sensitivity of human bladder cancer cells to urinary isoflavones.

Soybean foods have been suggested to be practical chemopreventives for human urinary tract cancers. Recently, we demonstrated that the co-operative action of isoflavones results in an increased dose-dependent growth inhibition and apoptosis than any single isoflavone compound. This study aimed to examine the potential of HER-2/neu as a biological target for soy isoflavones. The sensitivity of the bladder cancer cell lines (n=7) to the isoflavones was inversely related to the amount of HER-2/neu expressed. By using HER-2/neu transfection experiments, all three stable transfectants showed a significant growth inhibition by the isoflavone mixture at concentrations attainable in normal adult urine. An increased inhibition of tyrosine phosphorylation of proteins immunoprecipitated by HER-2/Neu was observed in the neu-transfectants compared with controls. The results of this study suggest that HER-2/neu may be a practical biochemical target for urinary isoflavones in vivo.