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dc.contributor.authorJin, Caining
dc.contributor.authorRajabi, Hasan Nabeel
dc.contributor.authorPitroda, Sean
dc.contributor.authorLi, Ailing
dc.contributor.authorKharbanda, Akriti
dc.contributor.authorWeichselbaum, Ralph
dc.contributor.authorKufe, Donald William
dc.date.accessioned2013-03-21T20:21:26Z
dc.date.issued2012
dc.identifier.citationJin, Caining, Hasan Rajabi, Sean Pitroda, Ailing Li, Akriti Kharbanda, Ralph Weichselbaum, and Donald Kufe. 2012. Cooperative interaction between the MUC1-C oncoprotein and the Rab31 GTPase in estrogen receptor-positive breast cancer cells. PLoS ONE 7(7): e39432.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10456100
dc.description.abstractRab31 is a member of the Ras superfamily of small GTPases that has been linked to poor outcomes in patients with breast cancer. The MUC1-C oncoprotein is aberrantly overexpressed in most human breast cancers and also confers a poor prognosis. The present results demonstrate that MUC1-C induces Rab31 expression in estrogen receptor positive (ER+) breast cancer cells. We show that MUC1-C forms a complex with estrogen receptor α (ERα) on the Rab31 promoter and activates Rab31 gene transcription in an estrogen-dependent manner. In turn, Rab31 contributes to the upregulation of MUC1-C abundance in breast cancer cells by attenuating degradation of MUC1-C in lysosomes. Expression of an inactive Rab31(S20N) mutant in nonmalignant breast epithelial cells confirmed that Rab31 regulates MUC1-C expression. The functional significance of the MUC1-C/Rab31 interaction is supported by the demonstration that Rab31 confers the formation of mammospheres by a MUC1-C-dependent mechanism. Analysis of microarray databases further showed that (i) Rab31 is expressed at higher levels in breast cancers as compared to that in normal breast tissues, (ii) MUC1+ and ER+ breast cancers have increased levels of Rab31 expression, and (iii) patients with Rab31-positive breast tumors have a significantly decreased ten-year overall survival as compared to those with Rab31-negative tumors. These findings indicate that MUC1-C and Rab31 function in an autoinductive loop that contributes to overexpression of MUC1-C in breast cancer cells.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0039432en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392244/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiochemistryen_US
dc.subjectProteinsen_US
dc.subjectProtein Interactionsen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCell Growthen_US
dc.subjectGene Expressionen_US
dc.subjectMedicineen_US
dc.subjectObstetrics and Gynecologyen_US
dc.subjectBreast Canceren_US
dc.subjectOncologyen_US
dc.subjectCancers and Neoplasmsen_US
dc.subjectBreast Tumorsen_US
dc.subjectInvasive Ductal Carcinomaen_US
dc.subjectBasic Cancer Researchen_US
dc.titleCooperative Interaction between the MUC1-C Oncoprotein and the Rab31 GTPase in Estrogen Receptor-Positive Breast Cancer Cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKufe, Donald William
dc.date.available2013-03-21T20:21:26Z
dc.identifier.doi10.1371/journal.pone.0039432*
dash.contributor.affiliatedKufe, Donald
dash.contributor.affiliatedRajabi, Hasan


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