title: Apoptosis induced by PGC-1β in breast cancer cells is mediated by the mTOR pathway.
abstract: The peroxisome proliferator-activated receptor-γ (PPAR-γ) coactivator-1β (PGC-1β) is a well-established regulator of mitochondrial biogenesis. However, the underlying mechanism of PGC-1β action remains elusive. This study reveals that knockdown of endogenous PGC-1β 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-1β, 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-1β 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-1β takes part in these events in breast cancer cells mediated by the mTOR signaling pathway.
authors.affiliation: Life Science College, Shaanxi Normal University, Xi'an 710062, P.R. China.
authors.forename: Libin
authors.initials: L
authors.lastname: Wang
authors.forename: Qilun
authors.initials: Q
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Heng
authors.initials: H
authors.lastname: Fan
authors.forename: Haibin
authors.initials: H
authors.lastname: Ma
authors.forename: Yongzhao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Ligang
authors.initials: L
authors.lastname: Wu
authors.forename: Xuebo
authors.initials: X
authors.lastname: Han
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Haibin
authors.initials: H
authors.lastname: Xia
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D000071186:Beclin-1; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D002352:Carrier Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C455622:PPARGC1B protein, human; C492571:RICTOR protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C463659:RPTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases