Activation of Murine Double Minute 2 by Akt in Mammary Epithelium Delays Mammary Involution and Accelerates Mammary Tumorigenesis

作者：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 B; Muller William J; Yu Dihua; Hung Mien Chie^*

来源：Cancer Research, 2010, 70(19): 7684-7689.

DOI：10.1158/0008-5472.CAN-09-3231

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 Ser(166) and Ser(186) 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. Cancer Res; 70(19); 7684-9.

• 出版日期2010-10-1
• 单位中国医科大学