| Literature DB >> 12032855 |
Sarah S Bacus1, Deborah A Altomare, Ljuba Lyass, Dot Mon Chin, Michael P Farrell, Katerina Gurova, Andrei Gudkov, Joseph R Testa.
Abstract
Amplification or overexpression of the HER-2/neu gene in breast cancers is associated with aggressive behavior and resistance to therapeutic regimens. The molecular mechanisms that contribute to therapeutic resistance/survival of HER-2/neu-overexpressing tumor cells have not been well defined. To determine if phosphatidylinositol 3-kinase/AKT signaling contributes to cell survival in HER-2/neu-positive breast cancers, we performed immunohistochemical analyses to evaluate expression of HER-2/neu and AKT in a series of 52 breast carcinomas. Elevated expression of HER-2/neu was found to correlate with overexpression of AKT2 protein and activation of AKT kinase. HER-2/neu-overexpressing breast cancer cell lines were resistant to apoptosis induced by UV treatment and hypoxia, which was suppressed in the presence of the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin, indicating a link between AKT activation and stress resistance in HER-2/neu-overexpressing cells. These observations suggest that AKT signaling augments resistance to stress-induced apoptosis in breast cancer cells overexpressing HER-2/neu.Entities:
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Year: 2002 PMID： 12032855 DOI： 10.1038/sj.onc.1205438
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867