Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis

Xiaoyun Cheng, Weiya Xia, Jer Yen Yang, Jennifer L. Hsu, Jing Yu Lang, Chao Kai Chou, Yi Du, Hui Lung Sun, Shannon L. Wyszomierski, Gordon B. Mills, William J. Muller, Dihua Yu, Mien Chie Hung

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    10 Scopus citations

    Abstract

    Amplification or overexpression of murine double minute 2 (MDM2) promotes a variety of human tumors by degrading tumor suppressor proteins such as p53. Phosphorylation of MDM2 on Ser166 and Ser186 by the survival kinase Akt inhibits p53-mediated apoptosis. However, it is unclear whether this pathway contributes to normal or malignant pathophysiology in vivo. To address these questions, we generated transgenic mice expressing the Akt-phosphorylated form of MDM2 (MDM2DDS166D/S186D) in the mammary epithelium. Activation of MDM2 delayed mammary gland involution and accelerated tumor progression in mouse mammary tumor virus/neu transgenic mice by inhibiting apoptosis in a manner associated with decreased p53 expression. Our findings offer in vivo evidence that activation of MDM2 by Akt contributes to mammary development and tumorigenesis.

    Original languageEnglish (US)
    Pages (from-to)7684-7689
    Number of pages6
    JournalCancer Research
    Volume70
    Issue number19
    DOIs
    StatePublished - Oct 1 2010

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Cheng, X., Xia, W., Yang, J. Y., Hsu, J. L., Lang, J. Y., Chou, C. K., Du, Y., Sun, H. L., Wyszomierski, S. L., Mills, G. B., Muller, W. J., Yu, D., & Hung, M. C. (2010). Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis. Cancer Research, 70(19), 7684-7689. https://doi.org/10.1158/0008-5472.CAN-09-3231