Authors

Zuoren Yu, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China ; Departments of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
Zengguang Xu, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Gabriele Disante, Department of Cancer Biology, Thomas Jefferson UniversityFollow
Jennifer Wright, Departments of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
Min Wang, Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Yuan Li, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Qian Zhao, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Tao Ren, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Xiaoming Ju, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Ellen Gutman, Departments of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
Guangxue Wang, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Sankar Addya, Kimmel Cancer Center, Department of Cancer Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Tieyan Li, Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China
Zhendong Xiang, People's Hospital of Gansu Province, Lanzhou, China
Chenguang Wang, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Xiongfei Yang, People's Hospital of Gansu Province, Lanzhou, China
Xiaolai Yang, People's Hospital of Gansu Province, Lanzhou, China
Richard Pestell, Departments of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PAFollow

Document Type

Article

Publication Date

4-2014

Comments

This article is the final published version in Oncotarget

Volume 5, Issue 4, April 2014, Pages 1083-1090.

The published version is available online.

Copyright © Impact Journals

Abstract

The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Herein, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse, demonstrates a requirement for Akt1 in miRNA-mediated cellular apoptosis. The miR-17/20 cluster is known to inhibit breast cancer cellular proliferation through G1/S cell cycle arrest via binding to the cyclin D1 3'UTR. Here we show that miR-17/20 overexpression sensitizes cells to apoptosis induced by either Doxorubicin or UV irradiation in MCF-7 cells via Akt1. miR-17/20 mediates apoptosis via increased p53 expression which promotes Akt degradation. Akt1-/- mammary epithelial cells which express Akt2 and Akt3 demonstrated increased apoptosis to DNA damaging agents. Akt1 deficiency abolished the miR-17/20-mediated apoptosis. These results demonstrated a novel pathway through which miR17/20 regulate p53 and Akt controlling breast cancer cell apoptosis.

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