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dc.contributor.authorKatz, E.
dc.contributor.authorDubois-Marshall, S.
dc.contributor.authorSims, A. H.
dc.contributor.authorFaratian, D.
dc.contributor.authorLi, J.
dc.contributor.authorSmith, E. S.
dc.contributor.authorQuinn, J. A.
dc.contributor.authorEdward, M.
dc.contributor.authorMeehan, R. R.
dc.contributor.authorEvans, E. E.
dc.contributor.authorLangdon, S. P.
dc.contributor.authorHarrison, David James
dc.date.accessioned2013-09-30T09:31:01Z
dc.date.available2013-09-30T09:31:01Z
dc.date.issued2010-07-27
dc.identifier.citationKatz , E , Dubois-Marshall , S , Sims , A H , Faratian , D , Li , J , Smith , E S , Quinn , J A , Edward , M , Meehan , R R , Evans , E E , Langdon , S P & Harrison , D J 2010 , ' A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk ' British Journal of Cancer , vol. 103 , no. 3 , pp. 401-410 . DOI: 10.1038/sj.bjc.6605763en
dc.identifier.issn0007-0920
dc.identifier.otherPURE: 23156586
dc.identifier.otherPURE UUID: cf782571-25d0-4bdf-8fca-9c0fd0b6dcc4
dc.identifier.otherWOS: 000280561300016
dc.identifier.otherScopus: 77955053214
dc.identifier.urihttp://hdl.handle.net/10023/4069
dc.description.abstractBACKGROUND: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown. METHODS: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro. RESULTS: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35. CONCLUSION: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers. British Journal of Cancer (2010) 103, 401-410. doi:10.1038/sj.bjc.6605763 www.bjcancer.com Published online 13 July 2010 (C) 2010 Cancer Research UKen
dc.format.extent10en
dc.language.isoeng
dc.relation.ispartofBritish Journal of Canceren
dc.rights(c) 2010 Cancer Research UK. This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectBreast canceren
dc.subjectC35en
dc.subjectHER2en
dc.subjectEpithelial to mesenchymal transitionen
dc.subjectITAMen
dc.subjectSyk kinaseen
dc.subjectRC0254 Neoplasms. Tumors. Oncology (including Cancer)en
dc.subject.lccRC0254en
dc.titleA gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syken
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.identifier.doihttps://doi.org/10.1038/sj.bjc.6605763
dc.description.statusPeer revieweden


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