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  • Original Paper
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AKT2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival

Oncogene volume 21, pages 3532–3540 (2002)Cite this article

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.

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Acknowledgements

This work has been supported by National Cancer Institute Grants CA77429 and CA06927, and by an appropriation from the Commonwealth of Pennsylvania.

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Author notes

  1. Sarah S Bacus and Deborah A Altomare: SS Bacus and DA Altomare contributed equally to this study

Authors and Affiliations

  1. Ventana Medical Systems, Inc./QDL, 610 Oakmont Lane, Westmont, 60559, Illinois, IL, USA

    Sarah S Bacus, Ljuba Lyass, Dot Mon Chin & Michael P Farrell

  2. Human Genetics Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, 19111, Pennsylvania, PA, USA

    Deborah A Altomare & Joseph R Testa

  3. Department of Molecular Biology, Lerner Research Institute, 9500 Euclid Avenue, Cleveland, 44195, Ohio, OH, USA

    Katerina Gurova & Andrei Gudkov

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  1. Sarah S Bacus
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  2. Deborah A Altomare
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Correspondence to Sarah S Bacus.

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Bacus, S., Altomare, D., Lyass, L. et al. AKT2 is frequently upregulated in HER-2/neu-positive breast cancers and may contribute to tumor aggressiveness by enhancing cell survival. Oncogene 21, 3532–3540 (2002). https://doi.org/10.1038/sj.onc.1205438

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