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dc.contributor.authorMorgado, Micaela
Sutton, Margie N.
Simmons, Mary
Warren, Curtis R.
Lu, Zhen
Constantinou, Pamela E.
Liu, Jinsong
Francis, Lewis L.W.
Conlan, R. Steven
Bast, Robert C. Jr.
Carson, Daniel D.
dc.date.accessioned 2016-06-06T16:48:22Z
dc.date.available 2016-06-06T16:48:22Z
dc.date.issued 2016
dc.identifier.citation Morgado, 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." Oncotarget, 7, no. 12 (2016) Impact Journals, LLC: 14871-14884. http://dx.doi.org/10.18632/oncotarget.7652.
dc.identifier.urihttps://hdl.handle.net/1911/90449
dc.description.abstract Transmembrane 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.
dc.language.iso eng
dc.publisher Impact Journals, LLC
dc.rights Article 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.
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.title Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
dc.type Journal article
dc.contributor.funder Rice University
dc.contributor.funder Rice University Fellowship Fund
dc.contributor.funder Rice University Institute of Biosciences and Bioenginnering Medical Innovation Fund
dc.contributor.funder National Cancer Institute
dc.contributor.funder Ovarian Cancer Research Fund
dc.contributor.funder National Foundation for Cancer Research
dc.contributor.funder National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers
dc.contributor.funder American Legion Auxiliary Fellowship in Cancer Research
dc.citation.journalTitle Oncotarget
dc.subject.keywordMUC16
CA125
cytokine
NF?B
cancer
dc.citation.volumeNumber 7
dc.citation.issueNumber 12
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.18632/oncotarget.7652
dc.identifier.pmid 26918940
dc.identifier.grantID P50 CA83639 (National Cancer Institute)
dc.identifier.grantID P30 CA16672 (National Cancer Institute)
dc.identifier.grantID TL1TR000369 (National Center for Advancing Translational Sciences of the National Institutes of Health)
dc.identifier.grantID UL1TR000371 (National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers)
dc.type.publication publisher version
dc.citation.firstpage 14871
dc.citation.lastpage 14884


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Article 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.
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