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Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells

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Abstract

c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

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Acknowledgements

This work was funded by the Seed Grant from City University of Hong Kong (Project Number 7004028), the National Natural Science Foundation of China (No. 81703753), the Research Fund of Zhejiang Chinese Medicine University (No. 2017ZR05), and the NSERC Discovery Grant NSERC (RGPIN-2015-04144).

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Authors and Affiliations

  1. Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diagnosis and Treatment of Digestive System Tumor, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, China

    Yiping Wang & Xiangdong Cheng

  2. Department of Biological Sciences, Xi’an Jiaotong-Liverpool University, 111 Ren’ai Road, Suzhou, 215123, China

    Muhammad Kaleem Samma & Sung Kay Chiu

  3. Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, 417 Apotex Center, 750 McDermot Avenue, Winnipeg, MB, R3E 0T5, Canada

    Sam K. P. Kung

  4. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York, NY, 10029, USA

    Clement M. Lee

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  1. Yiping Wang
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Correspondence to Sung Kay Chiu.

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Wang, Y., Cheng, X., Samma, M.K. et al. Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells. Mol Cell Biochem 443, 193–204 (2018). https://doi.org/10.1007/s11010-017-3224-5

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