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

Research output: Contribution to journalArticle

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
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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