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dc.contributor.authorGill, Jason H.*
dc.contributor.authorSeargent, Jill M.*
dc.contributor.authorYates, Elisabeth A.*
dc.date.accessioned2009-07-13T13:11:50Z
dc.date.available2009-07-13T13:11:50Z
dc.date.issued2004
dc.identifier.citationSeargent, J.H., Yates, E.A. and Gill, J.H. (2004). GW9662, an antagonist of PPAR-gamma, inhibits breast tumour cell growth and promotes the anticancer effects of the PPAR-gamma agonist Rosiglitazone, independently of PPAR-gamma activation. British Journal of Pharmacology. Vol. 143, No. 8, pp. 933-937.en
dc.identifier.urihttp://hdl.handle.net/10454/2987
dc.descriptionNoen
dc.description.abstractPeroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, is activated by several compounds, including the thiazolidinediones. In addition to being a therapeutic target for obesity, hypolipidaemia and diabetes, perturbation of PPARgamma signalling is now believed to be a strategy for treatment of several cancers, including breast. Although differential expression of PPARgamma is observed in tumours compared to normal tissues and PPARgamma agonists have been shown to inhibit tumour cell growth and survival, the interdependence of these observations is unclear. This study demonstrated that the potent, irreversible and selective PPARgamma antagonist GW9662 prevented activation of PPARgamma and inhibited growth of human mammary tumour cell lines. Controversially, GW9662 prevented rosiglitazone-mediated PPARgamma activation, but enhanced rather than reversed rosiglitazone-induced growth inhibition. As such, these data support the existence of PPARgamma-independent pathways and question the central belief that PPARgamma ligands mediate their anticancer effects via activation of PPARgamma.en
dc.language.isoenen
dc.subjectBreast canceren
dc.subjectGW9662en
dc.subjectPeroxisome proliferator-activated receptor (PPAR)en
dc.subjectPPAR¿en
dc.subjectRosiglitazoneen
dc.titleGW9662, an antagonist of PPAR-gamma, inhibits breast tumour cell growth and promotes the anticancer effects of the PPAR-gamma agonist Rosiglitazone, independently of PPAR-gamma activation.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen
dc.identifier.doihttps://doi.org/10.1038/sj.bjp.0705973


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