Apoptosis induced by PGC-1β in breast cancer cells is mediated by the mTOR pathway

作者：Wang, Libin; Liu, Qilun; Li, Fang; Qiu, Jing; Fan, Heng; Ma, Haibin; Zhu, Yongzhao; Wu, Ligang; Han, Xuebo; Yang, Zhihong; Jiang, Haifeng; Wei, Jun; Xia, Haibin^*

来源：Oncology Reports, 2013, 30(4): 1631-1638.

DOI：10.3892/or.2013.2628

• peroxisome proliferator-activated receptor-gamma coactivator-1 beta
• MDA-MB-231
• mammalian target of rapamycin pathway
• apoptosis

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) coactivator-1 beta (PGC-1 beta) is a well-established regulator of mitochondrial biogenesis. However, the underlying mechanism of PGC-1 beta action remains elusive. This study reveals that knockdown of endogenous PGC-1 beta by shorthairpin RNA (shRNA) leads to a decrease in the expression of mammalian target of rapamycin (mTOR) pathway-related genes in MDA-MB-231 cells. After knockdown of PGC-1 beta, phosphorylation of AMP-activated protein kinase (AMPK), phosphorylation of Rictor on Thr1135, Raptor and S6 protein was inhibited. However, Akt phosphorylation on Ser473 was upregulated and cell apoptosis occurred. In particular, we demonstrate that the levels of PGC-1 beta and mTOR correlated with overall mitochondrial activity. These results provide new evidence that cell apoptosis is orchestrated by the balance between several signaling pathways, and that PGC-1 beta takes part in these events in breast cancer cells mediated by the mTOR signaling pathway.

• 出版日期2013-10
• 单位宁夏医科大学; 陕西师范大学; 宁夏回族自治区人民医院; 青岛市市立医院