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

Resultado de la investigación: Articlerevisión exhaustiva

12 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)7684-7689
Número de páginas6
PublicaciónCancer Research
Volumen70
N.º19
DOI
EstadoPublished - oct. 1 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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