TY - JOUR
T1 - Circadian gene mPer2 overexpression induces cancer cell apoptosis
AU - Hua, Hui
AU - Wang, Yueqi
AU - Wan, Chaomin
AU - Liu, Yanyou
AU - Zhu, Bin
AU - Yang, Chunlei
AU - Wang, Xiaojia
AU - Wang, Zhengrong
AU - Cornelissen-Guillaume, Germaine G
AU - Halberg, Franz
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1349-7006.2006.00225.x
DO - 10.1111/j.1349-7006.2006.00225.x
M3 - Article
C2 - 16827798
AN - SCOPUS:33745941964
SN - 1347-9032
VL - 97
SP - 589
EP - 596
JO - Cancer Science
JF - Cancer Science
IS - 7
ER -