Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis
Page, C.; Lin, H.J.; Jin, Y.; Castle, V.P.; Nunez, G.; Huang, M.; Lin, J.
Anticancer Research 20(1a): 407-416
2000
ISSN/ISBN: 0250-7005 PMID: 10769688 Document Number: 516282
The AKT oncogenes are amplified or AKT kinase activity is constitutively elevated in several types of human malignancy. We sought to determine whether AKT might play a role in the development of resistance to apoptosis induced by chemotherapy. We showed that ovarian cancer cells either overexpressing constitutively active Akt/AKT1 or containing AKT2 gene amplification were highly resistant to paclitaxel than cancer cells express low AKT levels. The Akt/AKT1 clones also contained higher levels of phospho-Bad protein than parental cells. Further, the complexes between the endogenous pro-apoptotic protein, Bad, and the anti- apoptotic protein, BC1-XL were undetectable in Akt/AKT1 clones. These results suggest that Akt/AKT1 expressed in these clones can phosphorylate Bad and prevent it from binding to Bc1- XL. Furthermore, overexpression of Akt/AKT1 can inhibit the release of cytochrome c induced by paclitaxel. Therefore, our findings provide evidence that aberrant expression or activation of AKT in cancer cells may confer resistance to paclitaxel.