dc.contributor.author | Gahete, Manuel D. | |
dc.contributor.author | Córdoba-Chaćon, José | |
dc.contributor.author | Hergueta-Redondo, Marta | |
dc.contributor.author | Martińez-Fuentes, Antonio J. | |
dc.contributor.author | Kineman, Rhonda D. | |
dc.contributor.author | Moreno Bueno, Gema | |
dc.contributor.author | Luque, Raúl M. | |
dc.contributor.author | Castaño, Justo P. | |
dc.contributor.other | UAM. Departamento de Bioquímica | es_ES |
dc.date.accessioned | 2015-06-18T12:58:34Z | |
dc.date.available | 2015-06-18T12:58:34Z | |
dc.date.issued | 2011-08-11 | |
dc.identifier.citation | Plos One 6.8 (2011): e23302 | en_US |
dc.identifier.issn | 1932-6203 (online) | en_US |
dc.identifier.uri | http://hdl.handle.net/10486/666911 | |
dc.description.abstract | The human ghrelin gene, which encodes the ghrelin and obestatin peptides, contains 5 exons (Ex), with Ex1-Ex4 encoding a 117 amino-acid (aa) preproprotein that is known to be processed to yield a 28-aa (ghrelin) and/or a 23-aa (obestatin) mature peptides, which possess biological activities in multiple tissues. However, the ghrelin gene also encodes additional peptides through alternative splicing or post-translational modifications. Indeed, we previously identified a spliced mRNA ghrelin variant in mouse (In2-ghrelin-variant), which is regulated in a tissue-dependent manner by metabolic status and may thus be of biological relevance. Here, we have characterized a new human ghrelin variant that contains Ex0-1, intron (In) 1, and Ex2 and lacks Ex3-4. This human In1-ghrelin variant would encode a new prepropeptide that conserves the first 12aa of native-ghrelin (including the Ser3-potential octanoylation site) but has a different C-terminal tail. Expression of In1-variant was detected in 22 human tissues and its levels were positively correlated with those of ghrelin-O-acyltransferase (GOAT; p = 0.0001) but not with native-ghrelin expression, suggesting that In1-ghrelin could be a primary substrate for GOAT in human tissues. Interestingly, levels of In1-ghrelin variant expression in breast cancer samples were 8-times higher than those of normal mammary tissue, and showed a strong correlation in breast tumors with GOAT (p = 0.0001), ghrelin receptor-type 1b (GHSR1b; p = 0.049) and cyclin-D3 (a cell-cycle inducer/proliferation marker; p = 0.009), but not with native-ghrelin or GHSR1a expression. Interestingly, In1-ghrelin variant overexpression increased basal proliferation of MDA-MB-231 breast cancer cells. Taken together, our results provide evidence that In1-ghrelin is a novel element of the ghrelin family with a potential pathophysiological role in breast cancer | en_US |
dc.description.sponsorship | This work has been supported by FPU-AP20052473 (Ministerio de Ciencia e Innovación to Manuel D. Gahete), FI06-00804 (Instituto de Salud Carlos III to
José Córdoba-Chacón), SAF2007-63075 (Ministerio de Ciencia e Innovación to Marta Hergueta-Redondo), NIDDK30677/VA-Merit-Award (National Institutes of
Health and Jesse Brown VA Medical Center to Rhonda D. Kineman), SAF2007-63075/FMM07 (Ministerio de Ciencia e Innovación to Gema Moreno-Bueno), RYC-
2007-00186/BFU2008-01136-BFI (Ramón y Cajal and Ministerio de Ciencia e Innovación to Raul M. Luque), and BIO-0139/CTS-01705/BFU2007-60180-BFI
(Ministerio de Ciencia e Innovacio´n and Junta de Andalucía to Justo P. Castaño | en_US |
dc.format.extent | 11 pag. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | en |
dc.publisher | Public Library of Science | en_US |
dc.relation.ispartof | Plos One | en_US |
dc.title | A novel human ghrelin variant (in1-ghrelin) and ghrelin-O-acyltransferase are overexpressed in breast cancer: Potential pathophysiological relevance | en_US |
dc.type | article | en |
dc.subject.eciencia | Medicina | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0023302 | es_ES |
dc.identifier.publicationfirstpage | e23302 | es_ES |
dc.identifier.publicationissue | 8 | es_ES |
dc.identifier.publicationlastpage | e23302 | es_ES |
dc.identifier.publicationvolume | 6 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en |
dc.facultadUAM | Facultad de Medicina | |