PMID- 23877360 OWN - NLM STAT- MEDLINE DCOM- 20140429 LR - 20220408 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 30 IP - 4 DP - 2013 Oct TI - Apoptosis induced by PGC-1beta in breast cancer cells is mediated by the mTOR pathway. PG - 1631-8 LID - 10.3892/or.2013.2628 [doi] AB - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) coactivator-1beta (PGC-1beta) is a well-established regulator of mitochondrial biogenesis. However, the underlying mechanism of PGC-1beta action remains elusive. This study reveals that knockdown of endogenous PGC-1beta by short-hairpin 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-1beta, 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-1beta 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-1beta takes part in these events in breast cancer cells mediated by the mTOR signaling pathway. FAU - Wang, Libin AU - Wang L AD - Life Science College, Shaanxi Normal University, Xi'an 710062, P.R. China. FAU - Liu, Qilun AU - Liu Q FAU - Li, Fang AU - Li F FAU - Qiu, Jing AU - Qiu J FAU - Fan, Heng AU - Fan H FAU - Ma, Haibin AU - Ma H FAU - Zhu, Yongzhao AU - Zhu Y FAU - Wu, Ligang AU - Wu L FAU - Han, Xuebo AU - Han X FAU - Yang, Zhihong AU - Yang Z FAU - Jiang, Haifeng AU - Jiang H FAU - Wei, Jun AU - Wei J FAU - Xia, Haibin AU - Xia H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130718 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (BECN1 protein, human) RN - 0 (Beclin-1) RN - 0 (Carrier Proteins) RN - 0 (MAP1LC3A protein, human) RN - 0 (Membrane Proteins) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Multiprotein Complexes) RN - 0 (PPARGC1B protein, human) RN - 0 (RICTOR protein, human) RN - 0 (RNA, Small Interfering) RN - 0 (RNA-Binding Proteins) RN - 0 (RPTOR protein, human) RN - 0 (Rapamycin-Insensitive Companion of mTOR Protein) RN - 0 (Regulatory-Associated Protein of mTOR) RN - 415SHH325A (Adenosine Monophosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Adaptor Proteins, Signal Transducing/metabolism MH - Adenosine Monophosphate/metabolism MH - Adenosine Triphosphate/metabolism MH - Apoptosis/*genetics MH - Apoptosis Regulatory Proteins/biosynthesis MH - Beclin-1 MH - Breast Neoplasms/*metabolism MH - Carrier Proteins/genetics/*metabolism MH - Female MH - HEK293 Cells MH - Humans MH - Mechanistic Target of Rapamycin Complex 1 MH - Membrane Proteins/biosynthesis MH - Microtubule-Associated Proteins/metabolism MH - Mitochondria/metabolism MH - Multiprotein Complexes/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA Interference MH - RNA, Small Interfering MH - RNA-Binding Proteins MH - Rapamycin-Insensitive Companion of mTOR Protein MH - Regulatory-Associated Protein of mTOR MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction/genetics MH - TOR Serine-Threonine Kinases/biosynthesis/*metabolism EDAT- 2013/07/24 06:00 MHDA- 2014/04/30 06:00 CRDT- 2013/07/24 06:00 PHST- 2013/02/17 00:00 [received] PHST- 2013/04/19 00:00 [accepted] PHST- 2013/07/24 06:00 [entrez] PHST- 2013/07/24 06:00 [pubmed] PHST- 2014/04/30 06:00 [medline] AID - 10.3892/or.2013.2628 [doi] PST - ppublish SO - Oncol Rep. 2013 Oct;30(4):1631-8. doi: 10.3892/or.2013.2628. Epub 2013 Jul 18.