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dc.contributor.authorPickard, Mark Ren
dc.contributor.authorGreen, Andrew Ren
dc.contributor.authorEllis, Ian Oen
dc.contributor.authorCaldas, Carlosen
dc.contributor.authorHedge, Vanessa Len
dc.contributor.authorMourtada-Maarabouni, Mirnaen
dc.contributor.authorWilliams, Gwyn Ten
dc.date.accessioned2011-09-12T12:53:13Z
dc.date.available2011-09-12T12:53:13Z
dc.date.issued2009-08-11en
dc.identifier.issn1465-5411
dc.identifier.urihttp://www.dspace.cam.ac.uk/handle/1810/238929
dc.description.abstractAbstract Introduction Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK). Methods We have used RNA interference to downregulate Fau and Bcl-G expression, both simultaneously and independently, in breast cancer cells in vitro to determine the importance of their roles in apoptosis. Expression of Fau, Bcl-G and MELK was measured by quantitative RT-PCR in breast cancer tissue and in matched breast epithelial tissue from the same patients. Expression data of these genes obtained using microarrays from a separate group of patients were related to patient survival in Kaplan–Meier analyses. Results siRNA-mediated downregulation of either Fau or Bcl-G expression inhibited apoptosis, and the inhibition produced by combining the two siRNAs was consistent with control of Bcl-G by Fau. Fau expression is significantly reduced in breast cancer tissue and this reduction is associated with poor patient survival, as predicted for a candidate breast cancer tumour suppressor. In addition, MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene. Bcl-G expression is reduced in breast cancer tissue but decreased Bcl-G expression showed no correlation with survival, indicating that the most important factors controlling Bcl-G activity are post-translational modification (by Fau and MELK) rather than the rate of transcription of Bcl-G itself. Conclusions The combination of in vitro functional studies with the analysis of gene expression in clinical breast cancer samples indicates that three functionally interconnected genes, Fau, Bcl-G and MELK, are crucially important in breast cancer and identifies them as attractive targets for improvements in breast cancer risk prediction, prognosis and therapy.
dc.titleDysregulated expression of Fau and MELK is associated with poor prognosis in breast canceren
dc.typeArticle
dc.date.updated2011-09-12T12:53:13Z
dc.description.versionRIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.en
dc.language.rfc3066en
dc.rights.holderPickard et al.; licensee BioMed Central Ltd.
prism.publicationDate2009en
dcterms.dateAccepted2009-08-11en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2009-08-11en
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.identifier.eissn1465-542X
rioxxterms.typeJournal Article/Reviewen


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