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phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway has recently emerged as a potential target for cancer therapy. mTOR signaling is activated in many tumor types. The activated mTOR kinase in a complex with raptor (mTORC1
Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Institute of Endocrinology and Metabolism and Felsenstein Medical Research Center, Sackler School of Medicine, Department of Internal Medicine E, Department of Endocrinology, Department of Neurosurgery, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel
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Introduction Rapamycin, a lipophilic macrolide produced by the bacterium Streptomyces hygroscopicus , was initially developed as an anti-fungal agent ( Sehgal et al . 1975 ), but was then found to possess immunosuppressive and anti
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proteins (Bad, caspase-9, and GSK3b), cell cycle inhibitors (p21 and p27), products of tumor suppressor genes (FOX proteins, p53), and induction of signaling through nuclear factor κB (NF-κB) or the mammalian target of rapamycin (mTOR) pathway ( Manning
Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
Institute of Medical Science
Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
Institute of Medical Science
Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
Institute of Medical Science
Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
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Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
Institute of Medical Science
Department of Medical Biophysics University of Toronto, Toronto, Ontario, Canada
Division of Neurosurgery Toronto Western Hospital, 399 Bathurst Street, 4W-439, Toronto, Ontario, Canada M5T 2S8
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Ontario, Canada
Endocrine Oncology Site Group Princess Margaret Hospital, Toronto, Ontario, Canada
Department of Laboratory Medicine and Pathobiology University of Toronto, Toronto, Ontario, Canada
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mTOR pathway involvement in PA tumorigenesis and as a target for medical therapy. Effects of rapamycin (and rapalog)-induced mTOR inhibition on PA cellular proliferation and viability Rapamycin (sirolimus) is an immunosuppressant and antiproliferative
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growth factor (VEGF) pathway, and inhibitors of the mammalian target of rapamycin (mTOR), which have shown promising activity in recent clinical studies ( Duran et al . 2007 , Kulke 2007 , Yao et al . 2008 , 2010 ). mTOR is a serine threonine kinase
Institute of Cell and Molecular Biology, Department of Molecular Carcinogenesis, Department of Nutritional Sciences, University of Texas at Austin, Austin, Texas 78712, USA
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Institute of Cell and Molecular Biology, Department of Molecular Carcinogenesis, Department of Nutritional Sciences, University of Texas at Austin, Austin, Texas 78712, USA
Institute of Cell and Molecular Biology, Department of Molecular Carcinogenesis, Department of Nutritional Sciences, University of Texas at Austin, Austin, Texas 78712, USA
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. 2006 ). Adiponectin levels also increase following bariatric surgery ( Yang et al . 2001 ). The energy balance-related hormones exert at least some of their effects through a common signaling intermediate, the mammalian target of rapamycin (mTOR
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-activated receptor α (PPARα) effects ( Yamauchi et al . 2002 , 2003 , Yoon et al . 2006 ). Activated AMPK inhibits enzymes that regulate protein, fatty acid, and triglyceride synthesis, including mammalian target of rapamycin (mTOR), acetyl-CoA carboxylase (ACC
The Ohio State Biochemistry Program, Department of Physiology and Cell Biology, Molecular Virology, Internal Medicine
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The Ohio State Biochemistry Program, Department of Physiology and Cell Biology, Molecular Virology, Internal Medicine
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The Ohio State Biochemistry Program, Department of Physiology and Cell Biology, Molecular Virology, Internal Medicine
The Ohio State Biochemistry Program, Department of Physiology and Cell Biology, Molecular Virology, Internal Medicine
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by Rapamycin increased NIS expression and NIS-mediated RAIU in PCCl3 cells under acute TSH stimulation ( de Souza et al . 2010 ). To date; however, the effects of LY294002, Akti-1/2, or Rapamycin on NIS modulation in thyroid cells under chronic TSH
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et al. 2003 ). Recently, the evidence of cross-talk between the mammalian target of rapamycin (mTOR) pathway and ER is emerging. deGraffenried et al. (2004) demonstrated that rapamycin restored Tam resistance in MCF-7 breast cancer cells
Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Department of Public Health and Cell Biology, Laboratory of Neuroembryology, Digestive and Liver Disease Unit, Department of Clinical and Molecular Medicine, ARC‐NET Research Center, Department of Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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instance, it induces mRNA translation through activation of the mammalian target of rapamycin (mTOR) serine/threonine kinase ( Gorrini et al . 2005 ). However, whether adhesion-induced activation of protein synthesis relies on SFKs and if it promotes