Publication: In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.
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Date
2015-03-04
Authors
Ibáñez-Costa, Alejandro
Gahete, Manuel D
Rivero-Cortés, Esther
Rincón-Fernández, David
Nelson, Richard
Beltrán, Manuel
de la Riva, Andrés
Japón, Miguel A
Venegas-Moreno, Eva
Gálvez, Ma Ángeles
Advisors
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Publisher
Nature Publishing Group
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Abstract
Pituitary 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.
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MeSH Terms
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Adenoma
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Pro-Opiomelanocortin::Adrenocorticotropic Hormone
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::RNA Processing, Post-Transcriptional::RNA Splicing::Alternative Splicing
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Molecular Probe Techniques::Immunoassay::Immunoblotting::Blotting, Western
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::CHO Cells
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Cricetinae
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP Kinases
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Ghrelin
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Growth Hormone
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Introns
Medical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides
Medical Subject Headings::Diseases::Endocrine System Diseases::Pituitary Diseases::Pituitary Neoplasms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Isoforms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-akt
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::RNA Interference
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Pro-Opiomelanocortin::Adrenocorticotropic Hormone
Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::RNA Processing, Post-Transcriptional::RNA Splicing::Alternative Splicing
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Molecular Probe Techniques::Immunoassay::Immunoblotting::Blotting, Western
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::CHO Cells
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Cricetinae
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Mitogen-Activated Protein Kinases::Extracellular Signal-Regulated MAP Kinases
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Ghrelin
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Growth Hormone
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Introns
Medical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides
Medical Subject Headings::Diseases::Endocrine System Diseases::Pituitary Diseases::Pituitary Neoplasms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Protein Isoforms
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Oncogene Proteins::Proto-Oncogene Proteins::Proto-Oncogene Proteins c-akt
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::RNA Interference
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain Reaction
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured
DeCS Terms
CIE Terms
Keywords
Adenoma, Corticotropina, Empalme alternativo, Animales, Apoptosis, Inmunotransferencia Western, Células CHO, Línea celular tumoral, Cricetinae, Cinasas MAP reguladas por señales extracelulares, Regulación de la expresión génica neoplásica, Ghrelina, Hormona del crecimiento, Humanos, Intrones, Datos de Secuencia Molecular, Péptidos, Neoplasias hipofisarias, Isoformas de proteínas, Proteínas protooncogénicas c-akt, Interferencia por ARN, Reacción en cadena de la polimerasa por transcriptasa inversa, Transducción de señales, Células tumorales cultivadas
Citation
Ibáñez-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; 5:8714