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dc.contributor.authorO'BYRNE, KENen
dc.date.accessioned2014-09-08T11:04:39Z
dc.date.available2014-09-08T11:04:39Z
dc.date.issued2013en
dc.date.submitted2013en
dc.identifier.citationYuen, HF, Gunasekharan, VK, Chan, KK, Zhang, SD, Platt-Higgins, A, Gately, K, O'Byrne, K, Fennell, DA, Johnston, PG, Rudland, PS, El-Tanani, M, RanGTPase: A Candidate for Myc-Mediated Cancer Progression, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 105, 7, 2013, 475-488en
dc.identifier.issn0027-8874en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/71221
dc.descriptionPUBLISHEDen
dc.description.abstractBACKGROUND: Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. METHODS: We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P < .001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts. CONCLUSIONS: Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.en
dc.format.extent475-488en
dc.language.isoenen
dc.relation.ispartofseriesJNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTEen
dc.relation.ispartofseries105en
dc.relation.ispartofseries7en
dc.rightsYen
dc.subjectCancer treatmenten
dc.titleRanGTPase: A Candidate for Myc-Mediated Cancer Progressionen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/obyrnekeen
dc.identifier.rssinternalid96246en
dc.identifier.doihttp://dx.doi.org/10.1093/jnci/djt028en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeCanceren


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