| First Author | Cheng X | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 19 | Pages | 7684-9 |
| PubMed ID | 20841468 | Mgi Jnum | J:164678 |
| Mgi Id | MGI:4834957 | Doi | 10.1158/0008-5472.CAN-09-3231 |
| Citation | Cheng X, et al. (2010) Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis. Cancer Res 70(19):7684-9 |
| abstractText | 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. |
