Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis

The AKT oncogenes are amplified or AKT kinase activity is constitutively el evated in several types of human malignancy. We sought to determine whether AKT might play a role in the development of resistance to apoptosis induce d by chemotherapy. We showed that ovarian cancer cells either overexpressin g constitutively active Akt/AKT1 or containing AKT2 gene amplification were highly resistant to paclitaxel than cancer cells express low AKT levels. T he Akt/AKT1 clones also contained higher levels of phospho-Bad protein than parental cells. Further, the complexes between the endogenous pro-apoptoti c protein, Bad, and the anti- apoptotic protein, BC1-XL were undetectable i n Akt/AKT1 clones. These results suggest that Akt/AKT1 expressed in these c lones can phosphorylate Bad and prevent it from binding to Bcl- XL. Further more, overexpression of Akt/AKT1 can inhibit the release of cytochrome c in duced by paclitaxel. Therefore, our findings provide evidence that aberrant expression or activation of AKT in cancer cells may confer resistance to p aclitaxel.