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dc.contributor.authorMorgan, Richard*
dc.contributor.authorBoxall, A.*
dc.contributor.authorHarrington, K.J.*
dc.contributor.authorSimpson, G.R.*
dc.contributor.authorMichael, A.*
dc.contributor.authorPandha, H.S.*
dc.date.accessioned2016-10-11T09:06:49Z
dc.date.available2016-10-11T09:06:49Z
dc.date.issued2014-12
dc.identifier.citationMorgan R, Boxall A, Harrington KJ et al. (2014) Targeting HOX transcription factors in prostate cancer. BMC Urology. 14: 17.en_US
dc.identifier.urihttp://hdl.handle.net/10454/9886
dc.descriptionYesen_US
dc.description.abstractBackground: The HOX genes are a family of transcription factors that help to determine cell and tissue identity during early development, and which are also over-expressed in a number of malignancies where they have been shown to promote cell proliferation and survival. The purpose of this study was to evaluate the expression of HOX genes in prostate cancer and to establish whether prostate cancer cells are sensitive to killing by HXR9, an inhibitor of HOX function. Methods: HOX function was inhibited using the HXR9 peptide. HOX gene expression was assessed by RNA extraction from cells or tissues followed by quantitative PCR, and siRNA was used to block the expression of the HOX target gene, cFos. In vivo modelling involved a mouse flank tumour induced by inoculation with LNCaP cells. Results: In this study we show that the expression of HOX genes in prostate tumours is greatly increased with respect to normal prostate tissue. Targeting the interaction between HOX proteins and their PBX cofactor induces apoptosis in the prostate cancer derived cell lines PC3, DU145 and LNCaP, through a mechanism that involves a rapid increase in the expression of cFos, an oncogenic transcription factor. Furthermore, disrupting HOX/PBX binding using the HXR9 antagonist blocks the growth of LNCaP tumours in a xenograft model over an extended period. Conclusion: Many HOX genes are highly over-expressed in prostate cancer, and prostate cancer cells are sensitive to killing by HXR9 both in vitro and in vivo. The HOX genes are therefore a potential therapeutic target in prostate cancer.en_US
dc.description.sponsorshipThe authors gratefully acknowledge the support of the Prostate Project charity (UK).en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1186/1471-2490-14-17en_US
dc.rights© 2014 Morgan et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.subjectProstate cancer; HXR9; HOX; PBXen_US
dc.titleTargeting HOX transcription factors in prostate canceren_US
dc.status.refereedYesen_US
dc.date.application2014-02-05
dc.typeArticleen_US
dc.type.versionpublished version paperen_US
refterms.dateFOA2018-07-25T13:41:49Z


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