RT Journal Article
T1 In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features
A1 Ibáñez Costa, Alejandro
A1 Gahete, Manuel D
A1 Rivero Cortés, Esther
A1 Rincón Fernández, David
A1 Nelson, Richard
A1 Beltrán, Manuel
A1 Beltrán, Manuel
A1 Riva, Andrés de la
A1 Japón, Miguel A.
A1 Venegas Moreno, Eva
A1 Gálvez, Mª Ángeles
A1 García Arnés, Juan A.
A1 Soto Moreno, Alfonso
A1 Morgan, Jennifer R.
A1 Tsomaia, Natia
A1 Culler, Michael D.
A1 Diéguez González, Carlos
A1 Castaño, Justo P.
A1 Luque, Raúl M.
AB 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.
PB Nature Publishing Group
YR 2015
FD 2015
LK http://hdl.handle.net/10347/22017
UL http://hdl.handle.net/10347/22017
LA eng
NO Ibáñez-Costa, A., Gahete, M., Rivero-Cortés, E. et al. In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features. Sci Rep 5, 8714 (2015). https://doi.org/10.1038/srep08714
NO This work has been funded by the following grants: BIO-0139, CTS-1406, PI-0639-2012, BFU2013-43282, PI13/00651, CIBERobn and Ayuda Merck Serono 2013 (to R.M.L. and J.P.C.); fellowship CTS-5051 (to A.I.C.), “Sara Borrell” program CD11/00276 (to M.D.G.). CIBER is an initiative of Instituto de Salud Carlos III, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain
DS Minerva
RD 27 abr 2026