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 Mills, William J. Muller, Dihua Yu, Mien Chie Hung

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

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Transgenic Mice
Carcinogenesis
Breast
Epithelium
Apoptosis
Mouse mammary tumor virus
Tumor Suppressor Proteins
Human Mammary Glands
Neoplasms
Phosphotransferases
Phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis. / Cheng, Xiaoyun; Xia, Weiya; Yang, Jer Yen; Hsu, Jennifer L.; Lang, Jing Yu; Chou, Chao Kai; Du, Yi; Sun, Hui Lung; Wyszomierski, Shannon L.; Mills, Gordon; Muller, William J.; Yu, Dihua; Hung, Mien Chie.

In: Cancer Research, Vol. 70, No. 19, 01.10.2010, p. 7684-7689.

Research output: Contribution to journalArticle

Cheng, X, Xia, W, Yang, JY, Hsu, JL, Lang, JY, Chou, CK, Du, Y, Sun, HL, Wyszomierski, SL, Mills, G, Muller, WJ, Yu, D & Hung, MC 2010, 'Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis', Cancer Research, vol. 70, no. 19, pp. 7684-7689. https://doi.org/10.1158/0008-5472.CAN-09-3231
Cheng, Xiaoyun ; Xia, Weiya ; Yang, Jer Yen ; Hsu, Jennifer L. ; Lang, Jing Yu ; Chou, Chao Kai ; Du, Yi ; Sun, Hui Lung ; Wyszomierski, Shannon L. ; Mills, Gordon ; Muller, William J. ; Yu, Dihua ; Hung, Mien Chie. / Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis. In: Cancer Research. 2010 ; Vol. 70, No. 19. pp. 7684-7689.
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AU - Sun, Hui Lung

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