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dc.contributor.authorShaw, Greg
dc.contributor.authorPrice, Anna M.
dc.contributor.authorKtori, Elena
dc.contributor.authorBisson, Isabelle
dc.contributor.authorPurkis, Patricia E.
dc.contributor.authorMcFaul, Siobhan
dc.contributor.authorOliver, R. Tim D
dc.contributor.authorProwse, David M.
dc.date.accessioned2015-07-02T13:51:05Z
dc.date.available2015-07-02T13:51:05Z
dc.date.issued2008-12-01
dc.identifier.citationShaw , G , Price , A M , Ktori , E , Bisson , I , Purkis , P E , McFaul , S , Oliver , R T D & Prowse , D M 2008 , ' Hedgehog Signalling in Androgen Independent Prostate Cancer ' European Urology , vol. 54 , no. 6 , pp. 1333-1343 . https://doi.org/10.1016/j.eururo.2008.01.070
dc.identifier.issn0302-2838
dc.identifier.otherPURE: 8695049
dc.identifier.otherPURE UUID: fa9c2519-e747-459a-8384-beafba5367ea
dc.identifier.otherScopus: 45849143363
dc.identifier.otherPubMed: 18262716
dc.identifier.urihttp://hdl.handle.net/2299/16125
dc.description.abstractObjectives: Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC). Methods: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. Results: AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3PCA3 expression and the length of androgen-ablation therapy. Conclusions: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.en
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofEuropean Urology
dc.rights/dk/atira/pure/core/openaccesspermission/open
dc.subjectAndrogen-independent prostate cancer
dc.subjectCirculating tumour cells
dc.subjectCyclopamine
dc.subjectHedgehog signaling
dc.subjectLNCaP
dc.subjectPTCH
dc.titleHedgehog Signalling in Androgen Independent Prostate Canceren
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Accepted Version
rioxxterms.versionAM
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.eururo.2008.01.070
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeopenAccess


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