• Open Access

Circadian gene mPer2 overexpression induces cancer cell apoptosis

Authors

  • Hui Hua,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Yueqi Wang,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Chaomin Wan,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Yanyou Liu,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Bin Zhu,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Chunlei Yang,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Xiaojia Wang,

    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Zhengrong Wang,

    Corresponding author
    1. Health Ministry Key Laboratory of Chronobiology, West China Medical Center, Sichuan University, Chengdu, 610041, China;
    2. State Key Laboratory of Biotherapy, West China Hospital, Chengdu, 610041, China; and
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  • Germaine Cornelissen–Guillaume,

    1. Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN 55455, USA
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  • Franz Halberg

    1. Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN 55455, USA
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To whom correspondence should be addressed. E-mail: wangzhengrong@126.com

Abstract

The Period2 gene, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. We examined whether overexpression of the mouse Period2 gene (mPer2) in tumor cells influences cell growth and induces apoptosis. Overexpression of PERIOD2 in the mouse Lewis lung carcinoma cell line (LLC) and mammary carcinoma cell line (EMT6) results in reduced cellular proliferation and rapid apoptosis, but not in NIH 3T3 cells. Overexpressed mPER2 also altered the expression of apoptosis-related genes. The mRNA and protein levels of c-Myc, Bcl-XL and Bcl-2 were downregulated, whereas the expression of p53 and bax was upregulated in mPER2-overexpressing LLC cells compared with control cells transferred with empty plasmid. Our results suggest that the circadian gene mPeriod2 may play an important role in tumor suppression by inducing apoptotic cell death, which is attributable to enhanced pro-apoptotis signaling and attenuated anti-apoptosis processes. (Cancer Sci 2006; 97: 589–596)

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