Pérez-Pérez, AntonioSánchez-Jiménez, FloraVilariño-García, Teresade la Cruz, LuisVirizuela, Juan ASánchez-Margalet, Víctor2016-10-032016-10-032016-07-14Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, de la Cruz L, Virizuela JA, Sánchez-Margalet V. Sam68 Mediates the Activation of Insulin and Leptin Signalling in Breast Cancer Cells. PLoS ONE. 2016; 11(7):e0158218http://hdl.handle.net/10668/2440Journal Article;Obesity is a well-known risk factor for breast cancer development in postmenopausal women. High insulin and leptin levels seem to have a role modulating the growth of these tumours. Sam68 is an RNA-binding protein with signalling functions that has been found to be overexpressed in breast cancer. Moreover, Sam68 may be recruited to insulin and leptin signalling pathways, mediating its effects on survival, growth and proliferation in different cellular types. We aimed to study the expression of Sam68 and its phosphorylation level upon insulin and leptin stimulation, and the role of Sam68 in the proliferative effect and signalling pathways that are activated by insulin or leptin in human breast adenocarcinoma cells. In the human breast adenocarcinoma cell lines MCF7, MDA-MB-231 and BT-474, Sam68 protein quantity and gene expression were increased upon leptin or insulin stimulation, as it was checked by qPCR and immunoblot. Moreover, both insulin and leptin stimulation promoted an increase in Sam68 tyrosine phosphorylation and negatively regulated its RNA binding capacity. siRNA was used to downregulate Sam68 expression, which resulted in lower proliferative effects of both insulin and leptin, as well as a lower activation of MAPK and PI3K pathways promoted by both hormones. These effects may be partly explained by the decrease in IRS-1 expression by down-regulation of Sam68. These results suggest the participation of Sam68 in both leptin and insulin receptor signaling in human breast cancer cells, mediating the trophic effects of these hormones in proliferation and cellular growth.enAdenocarcinomaNeoplasias de la mamaRegulación negativaHiperinsulinismoLeptinaObesidadFosfatidilinositol 3-quinasasFosforilaciónPosmenopausiaMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::AdenocarcinomaMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-RegulationMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::HyperinsulinismMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::LeptinMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Phosphatidylinositol 3-Kinases::Phosphatidylinositol 3-KinaseMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::PhosphorylationMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::PostmenopauseMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::RNA, Small InterferingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::RNA-Binding ProteinsMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, InsulinMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids::Amino Acids, Cyclic::Amino Acids, Aromatic::Tyrosineresearch article27415018open access10.1371/journal.pone.01582181932-6203PMC4944952