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Start Over Descriptor "Serina-treonina quinasas TOR" Topic internal medicine
3 results on '"Serina-treonina quinasas TOR"'

1. Direct regulation of fibroblast growth factor 23 by energy intake through mTOR

Author

Mariano Rodriguez, Carmen Pineda, Ignacio González López, Escolastico Aguilera-Tejero, Rafael Rios, Ana I. Raya, Angela Vidal, Juan R. Muñoz-Castañeda, [Vidal,A, Rios,R, Pineda,C, Lopez,I, Aguilera-Tejero,E, Raya,AI] Department of Animal Medicine and Surgery, University of Cordoba, Campus Universitario Rabanales, Cordoba, Spain. [Vidal,A, Muñoz-Castañeda,JR, Rodriguez,M, Raya,AI] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain., and The work reported here was supported by a Spanish Government Grant from the Instituto de Salud Carlos III (PI17/00169) with co-financing from European Funds.

Subjects
0301 basic medicine, Fibroblast growth factor 23, Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings], Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings], lcsh:Medicine, 030204 cardiovascular system & hematology, Intestinal absorption, Endocrinology, 0302 clinical medicine, Organisms::Eukaryota::Animals [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, Wistar [Medical Subject Headings], lcsh:Science, Serina-treonina quinasas TOR, Factores de crecimiento de fibroblastos 23, Multidisciplinary, biology, Chemistry, TOR Serine-Threonine Kinases, Ingestión de energía, Endocrine system and metabolic diseases, Phosphorus, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Energy Intake [Medical Subject Headings], Female, Mannitol, medicine.drug, medicine.medical_specialty, RNA, messenger, Cells, Article, 03 medical and health sciences, Ratas, Células, In vivo, Internal medicine, Cell Line, Tumor, medicine, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::TOR Serine-Threonine Kinases [Medical Subject Headings], Animals, Rats, Wistar, Mechanistic target of rapamycin, PI3K/AKT/mTOR pathway, Messenger RNA, ARN mensajero, lcsh:R, Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Fibroblast Growth Factors [Medical Subject Headings], In vitro, Rats, Fibroblast Growth Factors, stomatognathic diseases, Fibroblast Growth Factor-23, 030104 developmental biology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings], Glucose, Check Tags::Female [Medical Subject Headings], Glucosa, Chemicals and Drugs::Inorganic Chemicals::Elements::Phosphorus [Medical Subject Headings], biology.protein, lcsh:Q, Energy Intake
Abstract

To test the hypothesis that fibroblast growth factor 23 (FGF23) is directly regulated by energy intake, in vivo and in vitro experiments were conducted. Three groups of rats were fed diets with high (HC), normal (NC) and low (LC) caloric content that resulted in different energy intake. In vitro, UMR106 cells were incubated in high (HG, 4.5 g/l) or low glucose (LG, 1 g/l) medium. Additional treatments included phosphorus (P), mannitol, rapamycin and everolimus. Intestinal absorption of P and plasma P concentrations were similar in the three groups of rats. As compared with NC, plasma FGF23 concentrations were increased in HC and decreased in the LC group. A significant correlation between energy intake and plasma FGF23 concentrations was observed. In vitro, mRNA FGF23 was significantly higher in UMR106 cells cultured in HG than in LG. When exposed to high P, mRNA FGF23 increased but only when cells were cultured in HG. Cells incubated with HG and mechanistic target of rapamycin (mTOR) inhibitors expressed low mRNA FGF23, similar to the values obtained in LG. In conclusion, this study shows a direct regulation of FGF23 production by energy availability and demonstrates that the mTOR signaling pathway plays a central role in this regulatory system.

Published
2020

2. Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans

Author

Enrique Saez, Joan Vendrell, Oscar Yanes, Sonia Fernández-Veledo, Marta Montori-Grau, Anna M. Gómez-Foix, Miriam Ejarque, Carolina Serena, Victoria Ceperuelo-Mallafré, Lourdes Garrido-Sánchez, Prasanth Puthanveetil, Miguel Angel Rodríguez, Catalina Núñez-Roa, Xavier Duran, Pablo M. Garcia-Roves, Kelly Roche, Francisco J. Tinahones, Alan R. Saltiel, [Ceperuelo-Mallafré,V, Ejarque,M, Serena,C, Núñez-Roa,C, Roche,K, Vendrell,J, Fernández-Veledo,S] Hospital Universitari de Tarragona Joan XXIII, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain. [Ceperuelo-Mallafré,V, Durán,X, Montori-Grau,M, Rodríguez,MA, Yánes,O, Gómez-Foix,AM, Fernández-Veledo,S] CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. [Montori-Grau,M] Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. [Rodríguez,MA] Centre for Omic Sciences (COS), Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Tarragona, Spain. [Yanes,O] Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain. [Puthanveetil,P, Saltiel,AR] Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. [Garrido-Sánchez,L, Tinahones,FJ] Hospital Universitario Virgen de la Victoria, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Universidad de Málaga, IBIMA, Spain. [Garrido-Sánchez,L, Tinahones,FJ] CIBER de Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Sáez,E] Department of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA. [García-Roves,PM] Departamento de Ciencias Fisiológicas II, Facultad de Medicina, Universitat de Barcelona, Barcelona, Spain., and This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2012-36186 to SF-V, PI14/00228 to JV and PI12/02355 to FJT). The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. SF-V and LG-S acknowledge support from the 'Miguel Servet' tenure-track program (CP10/00438 and CP13/00188, respectively) from the Fondo de Investigación Sanitaria (FIS) co-financed by the European Regional Development Fund (ERDF).

Subjects
0301 basic medicine, Macròfags, Physiology, Macrophage, Obesidad, Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings], Adipose tissue, White adipose tissue, Índice de masa corporal, Grasa subcutánea, Energy homeostasis, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], chemistry.chemical_compound, Adipocyte, Organisms::Eukaryota::Animals [Medical Subject Headings], Glucógeno sintasa, Masculino, Glycogen, Ratón, Humanos, Estrés fisiológico, Anatomy::Cells::Connective Tissue Cells::Adipocytes [Medical Subject Headings], Obesitat, Original Article, medicine.symptom, Anatomy::Tissues::Connective Tissue::Adipose Tissue::Adipose Tissue, White::Subcutaneous Fat [Medical Subject Headings], Resistència a la insulina, medicine.medical_specialty, lcsh:Internal medicine, Check Tags::Male [Medical Subject Headings], Inflammation, Context (language use), Biology, Resistencia a la insulina, Serina-Treonina Quinasas TOR, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Spectrum Analysis::Magnetic Resonance Spectroscopy [Medical Subject Headings], 03 medical and health sciences, Insulin resistance, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism::Insulin Resistance [Medical Subject Headings], Autofàgia, Internal medicine, Adipocitos, medicine, Autophagy, Obesity, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy [Medical Subject Headings], lcsh:RC31-1245, Molecular Biology, Espectrometría de Masas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Macrophages, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Glycosyltransferases::Hexosyltransferases::Glucosyltransferases::Glycogen Synthase [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Physiological Processes::Stress, Physiological [Medical Subject Headings], Espectroscopía de Resonancia Magnética, Cell Biology, medicine.disease, Glicogen, 030104 developmental biology, Endocrinology, chemistry, Animales, Glucosa, Biochemistry and Cell Biology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::TOR Serine-Threonine Kinases [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings]
Abstract

Objective Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. Methods We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. Results We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression. Conclusion Our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity., Highlights • Hypoxia redirects extracellular glucose to glycogen synthesis in human adipocytes. • Glycogen modifies the endocrine function of adipocytes and induces insulin resistance. • Glycogen stimulates leptin secretion through an autophagy-dependent mechanism. • Enforced glycogen accumulation in macrophages promotes M1 polarization. • Obesity is associated with higher GS expression and glycogen stores in adipose tissue.

Published
2015

3. Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

Author

Laudina Rodríguez, Anika Hüsing, Isabelle Romieu, Rudolf Kaaks, Naomi E. Allen, Heiner Boeing, Federico Canzian, Carlotta Sacerdote, Kim Overvad, Núria Sala, David G. Cox, Elio Riboli, José María Huerta, Henk J. van Kranen, Lucie Dostal, H. Bas Bueno-de-Mesquita, Jane Nautrup Østergaard, Afshan Siddiq, Ruth C. Travis, María José Sánchez, Nerea Larrañaga, Anne Tjønneland, Angelika Stein, Göran Hallmans, Nicholas J. Wareham, Daniele Campa, Antonia Trichopoulou, Nina Roswall, Rosario Tumino, Pagona Lagiou, Mazda Jenab, Dimitrios Trichopoulos, Aurelio Barricarte, Mattias Johansson, Kay-Tee Khaw, Domenico Palli, Tobias Pischon, Sabina Sieri, [Campa, Daniele, Huesing, Anika, Stein, Angelika, Dostal, Lucie, Canzian, Federico, Kaaks, Rudolf] German Canc Res Ctr, Heidelberg, Germany. [Boeing, Heiner, Pischon, Tobias] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany. [Tjonneland, Anne, Roswall, Nina] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Overvad, Kim, Ostergaard, Jane Nautrup] Aarhus Univ Hosp, Dept Cardiol, Cardiovasc Res Ctr, Aalborg Hosp, Aalborg, Denmark. [Overvad, Kim, Ostergaard, Jane Nautrup] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, DK-8000 Aarhus C, Denmark. [Rodriguez, Laudina] Hlth & Hlth Care Serv Council, Publ Hlth & Participat Directorate, Asturias, Spain. [Sala, Nuria] ICO IDIBELL, Barcelona, Spain. [Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain. [Sanchez, Maria-Jose, Larranaga, Nerea, Maria Huerta, Jose, Barricarte, Aurelio] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid, Spain. [Larranaga, Nerea] Basque Govt, Publ Hlth Dept Gipuzkoa, Gipuzkoa, Spain. [Maria Huerta, Jose] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain. [Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain. [Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Cambridge, England. [Wareham, Nicholas] MRC Epidemiol Unit, Cambridge, England. [Travis, Ruth C., Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Lagiou, Pagona, Trichopoulou, Antonia] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, GR-11527 Athens, Greece. [Lagiou, Pagona, Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Trichopoulou, Antonia] Hellen Hlth Fdn, Athens, Greece. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Sieri, Sabina] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Histopathol Unit, Ragusa, Italy. [Sacerdote, Carlotta] Ctr Canc Prevent CPO Piemonte, Turin, Italy. [Sacerdote, Carlotta] Human Genet Fdn HuGeF, Turin, Italy. [van Kranen, Henk, Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth CVG, Bilthoven, Netherlands. [Hallmans, Goran, Johansson, Mattias] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Johansson, Mattias, Romieu, Isabelle, Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Cox, David G., Siddiq, Afshan, Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England. [Cox, David G.] Ctr Leon Berard, INSERM, F-69373 Lyon, France., Specific results of this study were obtained with financial support from the US Army Medical Research and Material Command (W81XWH-05-1-0156). http://cdmrp.army.mil/pcrp/default.shtml. The EPIC study was funded by 'Europe Against Cancer' Programme of the European Commission (SANCO), Ligue contre le Cancer (France), Société 3M (France), Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM), German Cancer Aid, German Cancer Research Center, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund (FIS) of the Spanish Ministry of Health, the participating regional governments and institutions of Spain, Cancer Research UK, Medical Research Council, UK, Hellenic Ministry of Health and Social Solidarity, the Stavros Niarchos Foundation and the Hellenic Health Foundation, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Ministry of Health, Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) (The Netherlands), Statistics Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane, Sweden, Norwegian Cancer Society, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), German Institute of Human Nutrition Potsdam-Rehbrücke, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Cancer Epidemiology Institute, Department of Cardiology, Aarhus University Hospital, Public Health and Participation Directorate, Health and Health Care Services Council, Catalan Institute of Oncology, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Granada Cancer Registry, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Authority, Public Health Institute of Navarra, School of Clinical Medicine, University of Cambridge [UK] (CAM), Epidemiology Unit, Medical Research Council, Cancer Epidemiology Unit, University of Oxford [Oxford]-Cancer Epidemiology Unit, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene-Epidemiology and Medical Statistics-Athens Medical School, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Cancer Registry, Civile - M.P.Arezzo Hospital, CPO Piemonte, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Unit of Nutrition, Environment, and Cancer, Equipe 6, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genomics of Common Disease, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, Department of Epidemiology and Public Health, Imperial College London, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Aalborg Hospital-Aarhus University Hospital, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública ( CIBERESP ), Andalusian School of Public Health, University of Cambridge [UK] ( CAM ), Azienda Ospedaliera 'Civile M.P.Arezzo', National Institute for Public Health and the Environment [Bilthoven] ( RIVM ), University of Umeå, International Agency for Research on Cancer, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Oncology, Male, MESH: Carcinoma, Epidemiology, protein p53, MESH : Aged, PROTEIN, Genome-wide association study, MESH : Genotype, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, KAPPA-B ACTIVATION, MESH: Genotype, 0302 clinical medicine, PKC-IOTA, Epidemiology of cancer, Multicenter Studies as Topic, TUBEROUS SCLEROSIS, MESH: Genetic Variation, lcsh:Science, MESH : Isoenzymes, 0303 health sciences, MESH: Middle Aged, MESH : Carcinoma, TOR Serine-Threonine Kinases, Cancer Risk Factors, target of rapamycin kinase, MTOR protein, MESH: Case-Control Studies, 3. Good health, 030220 oncology & carcinogenesis, Medicine, Science & Technology - Other Topics, MESH : Genome-Wide Association Study, Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], MESH : Prostatic Neoplasms, Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Signal Transduction [Medical Subject Headings], medicine.medical_specialty, MESH : Case-Control Studies, Genotype, Single-nucleotide polymorphism, Variación genética, 03 medical and health sciences, Genetics, Cancer Genetics, Humans, MESH : Middle Aged, human, Biology, mammalian target of rapamycin, Aged, Estudio Multicéntrico, Science & Technology, MESH: Humans, MULTIDISCIPLINARY SCIENCES, lcsh:R, MESH : Humans, Genetic Variation, medicine.disease, MESH : Neoplasms, Genitourinary Tract Tumors, Genetic epidemiology, Cardiovascular and Metabolic Diseases, Case-Control Studies, KINASE-C-IOTA, MESH: Genome-Wide Association Study, MESH: Multicenter Studies as Topic, lcsh:Q, MESH : Genetic Predisposition to Disease, RAPAMYCIN, Lifestyle Causes of Cancer, MESH: Signal Transduction, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings], lcsh:Medicine, Bioinformatics, MESH : Multicenter Studies as Topic, Prostate cancer, Risk Factors, MESH: Risk Factors, Neoplasms, Clinical Epidemiology, MESH: Neoplasms, Protein Kinase C, MESH: Aged, Multidisciplinary, Prostate Cancer, MESH: Genetic Predisposition to Disease, Middle Aged, MESH : Risk Factors, European Prospective Investigation into Cancer and Nutrition, Europe, Isoenzymes, Diseases::Male Urogenital Diseases::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Genetic Epidemiology, protein kinase C lambda, MESH: Isoenzymes, MESH : TOR Serine-Threonine Kinases, isoenzyme, Cancer Epidemiology, Signal Transduction, Research Article, MESH : Male, Genetic Causes of Cancer, MESH : Europe, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neoplasias de la Próstata, Genetic polymorphisms, Serina-Treonina Quinasas TOR, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings], LUNG-CANCER, MESH : Genetic Variation, Internal medicine, medicine, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::TOR Serine-Threonine Kinases [Medical Subject Headings], Genetic Predisposition to Disease, MESH : Protein Kinase C, PI3K/AKT/mTOR pathway, Genetic Association Studies, MESH: TOR Serine-Threonine Kinases, 030304 developmental biology, MESH : Signal Transduction, COMPLEX, Càncer de pròstata, Polimorfisme genètic, Carcinoma, MTOR protein, human, protein kinase C, Cancer, Prostatic Neoplasms, Cancers and Neoplasms, Human Genetics, MESH: Protein Kinase C, MESH: Male, MAMMALIAN TARGET, MESH: Prostatic Neoplasms, CELL-GROWTH, MESH: Europe, EPIC, Genome-Wide Association Study
Abstract

International audience; The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p

Published
2011

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