Circadian gene mPer2 overexpression induces cancer cell apoptosis
Circadian gene mPer2 overexpression induces cancer cell apoptosis
复制标题
DOI：
10.1111/j.1349-7006.2006.00225.x
复制
发表时间：
2006-07-01
期刊：
影响因子：
5.7
通讯作者：
Halberg, Franz
中科院分区：
文献类型：
--
作者：
Hua, Hui;Wang, Yueqi;Halberg, Franz
周期蛋白2基因是生物钟中不可缺少的组成部分，它不仅调节生物钟的昼夜振荡，而且还调节机体的功能。我们检测了小鼠周期蛋白2基因(MPer2)在肿瘤细胞中的过表达是否影响细胞生长和诱导细胞凋亡。在小鼠Lewis肺癌细胞系(LLC)和乳腺癌细胞系(EMT6)中过表达Perod2导致细胞增殖减少和快速凋亡，但对NIH3T3细胞没有影响。过表达的mPER2也改变了凋亡相关基因的表达。与空白对照细胞相比，mPER2高表达的LLC细胞c-Myc、BclX-L和Bcl2mRNA和蛋白表达下调，而P53和Bax表达上调。我们的结果表明，昼夜节律基因mPerod2可能通过诱导凋亡细胞死亡而在肿瘤抑制中发挥重要作用，这归因于促凋亡信号的增强和抗凋亡过程的减弱。
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-X-L 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.