Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB

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dc.citation.firstpage14871en_US
dc.citation.issueNumber12en_US
dc.citation.journalTitleOncotargeten_US
dc.citation.lastpage14884en_US
dc.citation.volumeNumber7en_US
dc.contributor.authorMorgado, Micaelaen_US
dc.contributor.authorSutton, Margie N.en_US
dc.contributor.authorSimmons, Maryen_US
dc.contributor.authorWarren, Curtis R.en_US
dc.contributor.authorLu, Zhenen_US
dc.contributor.authorConstantinou, Pamela E.en_US
dc.contributor.authorLiu, Jinsongen_US
dc.contributor.authorFrancis, Lewis L.W.en_US
dc.contributor.authorConlan, R.Stevenen_US
dc.contributor.authorBast, Robert C.Jr.en_US
dc.contributor.authorCarson, Daniel D.en_US
dc.date.accessioned2016-06-06T16:48:22Zen_US
dc.date.available2016-06-06T16:48:22Zen_US
dc.date.issued2016en_US
dc.description.abstractTransmembrane mucins (TMs) are restricted to the apical surface of normal epithelia. In cancer, TMs not only are over-expressed, but also lose polarized distribution. MUC16/CA125 is a high molecular weight TM carrying the CA125 epitope, a well-known molecular marker for human cancers. MUC16 mRNA and protein expression was mildly stimulated by low concentrations of TNFα (2.5 ng/ml) or IFNγ (20 IU/ml) when used alone; however, combined treatment with both cytokines resulted in a moderate (3-fold or less) to large (> 10-fold) stimulation of MUC16 mRNA and protein expression in a variety of cancer cell types indicating that this may be a general response. Human cancer tissue microarray analysis indicated that MUC16 expression directly correlates with TNFα and IFNγ staining intensities in certain cancers. We show that NFκB is an important mediator of cytokine stimulation of MUC16 since siRNA-mediated knockdown of NFκB/p65 greatly reduced cytokine responsiveness. Finally, we demonstrate that the 250 bp proximal promoter region of MUC16 contains an NFκB binding site that accounts for a large portion of the TNFα response. Developing methods to manipulate MUC16 expression could provide new approaches to treating cancers whose growth or metastasis is characterized by elevated levels of TMs, including MUC16.en_US
dc.identifier.citationMorgado, Micaela, Sutton, Margie N., Simmons, Mary, et al.. "Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB." <i>Oncotarget,</i> 7, no. 12 (2016) Impact Journals, LLC: 14871-14884. http://dx.doi.org/10.18632/oncotarget.7652.en_US
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.7652en_US
dc.identifier.urihttps://hdl.handle.net/1911/90449en_US
dc.language.isoengen_US
dc.publisherImpact Journals, LLCen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.subject.keywordMUC16en_US
dc.subject.keywordCA125en_US
dc.subject.keywordcytokineen_US
dc.subject.keywordNF?Ben_US
dc.subject.keywordcanceren_US
dc.titleTumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκBen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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