Ibáñez-Costa, AlejandroGahete, Manuel DRivero-Cortés, EstherRincón-Fernández, DavidNelson, RichardBeltrán, Manuelde la Riva, AndrésJapón, Miguel AVenegas-Moreno, EvaGálvez, Ma ÁngelesGarcía-Arnés, Juan ASoto-Moreno, AlfonsoMorgan, JenniferTsomaia, NatiaCuller, Michael DDieguez, CarlosCastaño, Justo PLuque, Raúl M2016-07-132016-07-132015-03-04Ibáñez-Costa A, Gahete MD, Rivero-Cortés E, Rincón-Fernández D, Nelson R, Beltrán M, et al. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features. Sci Rep. 2015; 5:8714http://hdl.handle.net/10668/2264Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas comparedwith normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24–72 h) increased GH and ACTH secretion, Ca2+ and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.enAdenomaCorticotropinaEmpalme alternativoAnimalesApoptosisInmunotransferencia WesternCélulas CHOLínea celular tumoralCricetinaeCinasas MAP reguladas por señales extracelularesRegulación de la expresión génica neoplásicaGhrelinaHormona del crecimientoHumanosIntronesDatos de Secuencia MolecularPéptidosNeoplasias hipofisariasIsoformas de proteínasProteínas protooncogénicas c-aktInterferencia por ARNReacción en cadena de la polimerasa por transcriptasa inversaTransducción de señalesCélulas tumorales cultivadasMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::AdenomaMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Pro-Opiomelanocortin::Adrenocorticotropic HormoneMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::RNA Processing, Post-Transcriptional::RNA Splicing::Alternative SplicingMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Molecular Probe Techniques::Immunoassay::Immunoblotting::Blotting, WesternMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::CHO CellsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::CricetinaeMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP KinasesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, NeoplasticMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::GhrelinMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Growth HormoneMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::IntronsMedical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence DataMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::PeptidesMedical Subject Headings::Diseases::Endocrine System Diseases::Pituitary Diseases::Pituitary NeoplasmsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein IsoformsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-aktMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::RNA InterferenceMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain ReactionMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Culturedresearch article25737012open access10.1038/srep087142045-2322PMC4649711