Research Papers:

miR-17/20 sensitization of breast cancer cells to chemotherapy-induced apoptosis requires Akt1

Zuoren Yu _, Zengguang Xu, Gabriele DiSante, Jennifer Wright, Min Wang, Yuan Li, Qian Zhao, Tao Ren, Xiaoming Ju, Ellen Gutman, Guangxue Wang, Sankar Addya, Tieyan Li, Zhendong Xiang, Chenguang Wang, Xiongfei Yang, Xiaolai Yang and Richard Pestell

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Oncotarget. 2014; 5:1083-1090. https://doi.org/10.18632/oncotarget.1804

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Zuoren Yu1,2, Zengguang Xu1, Gabriele DiSante2, Jennifer Wright2, Min Wang2, Yuan Li1, Qian Zhao1, Tao Ren1, Xiaoming Ju2, Ellen Gutman2, Guangxue Wang1, Sankar Addya2, Tieyan Li1, Zhendong Xiang3, Chenguang Wang2, Xiongfei yang3, Xiaolai Yang3, Richard Pestell2

1 Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education, East Hospital, Tongji University School of Medicine, Shanghai, China,

2 Departments of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA

3 People’s Hospital of Gansu Province, Lanzhou, China


Richard G. Pestell, email:

Zuoren Yu, email:

Keywords: miR-17/20, breast cancer, AKT, apoptosis

Received: January 29, 2014 Accepted: March 2, 2014 Published: March 4, 2014


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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