A novel human ghrelin variant (in1-ghrelin) and ghrelin-O-acyltransferase are overexpressed in breast cancer: Potential pathophysiological relevance

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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

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