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Medientyp: E-Artikel Titel: Activation of Murine Double Minute 2 by Akt in Mammary Epithelium Delays Mammary Involution and Accelerates Mammary Tumorigenesis Beteiligte: 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 Erschienen: American Association for Cancer Research (AACR), 2010 Erschienen in: Cancer Research, 70 (2010) 19, Seite 7684-7689 Sprache: Englisch DOI: 10.1158/0008-5472.can-09-3231 ISSN: 0008-5472; 1538-7445 Schlagwörter: Cancer Research ; Oncology Entstehung: Anmerkungen: Beschreibung: <jats:title>Abstract</jats:title> <jats:p>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. Cancer Res; 70(19); 7684–9. ©2010 AACR.</jats:p> Zugangsstatus: Freier Zugang