Saccharomyces Cerevisiae

Indianapolis, IN

The phosphatidylinositol 3'-kinase (PI3K) growth signaling pathway results in many changes in the cell ultimately leading to cell growth, cell cycle entry, cell migration, and cell survival. PI3K activation by growth factor results in the recruitment and activation of a wide range of signaling factors to the cellular membrane, which then regulate gene expression. We have shown that activation of the PI3K pathway leads to over-expression of enhancer of Zeste homolog (EZH2) in UMUC3 bladder cancer and UMUC14 urothelial cancer cell lines. EZH2 is the primary histone methyltransferase of histone 3 at lysine 27 (H3K27) and has been implicated in increased invasiveness and increased mortality in breast and prostate cancers when over-expressed. In this study, the effect of EZH2 knockdown on cell growth and proliferation has been assessed. Our results have shown that when EZH2 expression is knocked down in UMUC3 and UMUC14 cell lines there is a significant decrease in cellular growth and proliferation when compared to cells treated with negative siRNA. As part of this study, the effect of EZH2 knockdown on invasiveness and the methylation status of H3K27 will also be examined. By understanding the effects of EZH2 expression on the cell we will then be able to deduce a mechanism by which it acts. If EZH2 is implicated in cancer then a treatment plan targeting this protein could be studied in order to improve the chance of survival for individuals affected by cancer involving EZH2 over-expression.