PMID- 22320865 OWN - NLM STAT- MEDLINE DCOM- 20120913 LR - 20240321 IS - 1557-7430 (Electronic) IS - 1044-5498 (Print) IS - 1044-5498 (Linking) VI - 31 IP - 6 DP - 2012 Jun TI - Inhibition of mammalian target of rapamycin signaling by CCI-779 (temsirolimus) induces growth inhibition and cell cycle arrest in Cashmere goat fetal fibroblasts (Capra hircus). PG - 1095-9 LID - 10.1089/dna.2011.1559 [doi] AB - The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase. It plays an evolutionarily conserved role in regulating cell growth, proliferation, survival, and metabolism via different cellular processes. The purpose of this study was to explore the inhibitory effects of CCI-779 (temsirolimus), a specific mTOR inhibitor, on mTOR signaling, and examine the mechanism of cell growth suppression by CCI-779 in Cashmere goat fetal fibroblasts (GFb cells). GFb cells were sensitive to CCI-779 and the survival rate of cells treated with >3.0 muM of CCI-779 was significantly reduced compared with the control (p<0.01). CCI-779 inhibited the phosphorylation of mTOR (at Ser2448) and S6 (at Ser240/244), and the expression of mTOR, p70S6K, and S6. Thus, CCI-779 was toxic to GFb cells, and it induced a dose-dependent decrease in cell proliferation and caused G1/S cell cycle arrest. Taken together, these data show that CCI-779 can inhibit mTOR signaling and proliferation in GFb cells in vitro. Therefore, mTOR is an important regulator for GFb cell growth and proliferation. FAU - Wang, Zhigang AU - Wang Z AD - The Key Laboratory of Mammal Reproductive Biology and Biotechnology, College of Life Science, Inner Mongolia University, Ministry of Education, Hohhot, PR China. lswzg@imu.edu.cn FAU - Liu, Taodi AU - Liu T FAU - Chen, Yuhao AU - Chen Y FAU - Zhang, Xin AU - Zhang X FAU - Liu, Mingtao AU - Liu M FAU - Fu, Haixia AU - Fu H FAU - Liu, Dongjun AU - Liu D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120209 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (Protein Kinase Inhibitors) RN - 624KN6GM2T (temsirolimus) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Cell Cycle Checkpoints/*drug effects MH - Enzyme Activation/drug effects MH - *Fetus MH - Fibroblasts/*cytology/drug effects/metabolism MH - G1 Phase Cell Cycle Checkpoints/drug effects MH - *Goats MH - Protein Kinase Inhibitors/pharmacology MH - Ribosomal Protein S6 Kinases, 70-kDa/metabolism MH - S Phase Cell Cycle Checkpoints/drug effects MH - Signal Transduction/*drug effects MH - Sirolimus/*analogs & derivatives/pharmacology MH - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism PMC - PMC3378953 EDAT- 2012/02/11 06:00 MHDA- 2012/09/14 06:00 PMCR- 2013/06/01 CRDT- 2012/02/11 06:00 PHST- 2012/02/11 06:00 [entrez] PHST- 2012/02/11 06:00 [pubmed] PHST- 2012/09/14 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - 10.1089/dna.2011.1559 [pii] AID - 10.1089/dna.2011.1559 [doi] PST - ppublish SO - DNA Cell Biol. 2012 Jun;31(6):1095-9. doi: 10.1089/dna.2011.1559. Epub 2012 Feb 9.