In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.
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 compared with 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, Ca(2+) 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.
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
Alejandro
A
Ibáñez-Costa
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
Manuel D
MD
Gahete
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
Esther
E
Rivero-Cortés
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
David
D
Rincón-Fernández
IPSEN Bioscience, Cambridge, 02142 Massachusetts, USA.
Richard
R
Nelson
Department of Pathology, Puerta del Mar University Hospital, Cádiz.
Manuel
M
Beltrán
Service of Neurosurgery, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain.
Andrés
A
de la Riva
Department of Pathology, Hospital Universitario Virgen del Rocío, 41013 Seville, Spain.
Miguel A
MA
Japón
Metabolism and Nutrition Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), 41013 Seville, Spain.
Eva
E
Venegas-Moreno
Service of Endocrinology and Nutrition, Hospital Universitario Reina Sofia, and Instituto Maimónides de Investigación Biomédica de Córdoba, 14004 Córdoba, Spain.
Ma Ángeles
MÁ
Gálvez
Department of Endocrinology and Nutrition, Carlos Haya Hospital, 29010 Málaga, Spain.
Juan A
JA
García-Arnés
Metabolism and Nutrition Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), 41013 Seville, Spain.
Alfonso
A
Soto-Moreno
IPSEN Bioscience, Cambridge, 02142 Massachusetts, USA.
Jennifer
J
Morgan
IPSEN Bioscience, Cambridge, 02142 Massachusetts, USA.
Natia
N
Tsomaia
IPSEN Bioscience, Cambridge, 02142 Massachusetts, USA.
Michael D
MD
Culler
Department of Physiology, University of Santiago de Compostela, and CIBER Fisiopatología de la Obesidad y Nutrición, 15782 Santiago de Compostela, Spain.
Carlos
C
Dieguez
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
Justo P
JP
Castaño
Department of Cell Biology, Physiology and Immunology, University of Cordoba, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofia; CIBER Fisiopatología de la Obesidad y Nutrición; and Campus de Excelencia Internacional Agroalimentario (ceiA3), 14014 Córdoba, Spain.
Raúl M
RM
Luque
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D054439:Ghrelin; D010455:Peptides; D020033:Protein Isoforms; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases