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

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...

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Autores principales: Morgado, Micaela, Sutton, Margie N., Simmons, Mary, Warren, Curtis R., Lu, Zhen, Constantinou, Pamela E., Liu, Jinsong, Francis, Lewis LW., Conlan, R. Steven, Bast, Robert C., Carson, Daniel D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924758/
https://www.ncbi.nlm.nih.gov/pubmed/26918940
http://dx.doi.org/10.18632/oncotarget.7652
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author Morgado, Micaela
Sutton, Margie N.
Simmons, Mary
Warren, Curtis R.
Lu, Zhen
Constantinou, Pamela E.
Liu, Jinsong
Francis, Lewis LW.
Conlan, R. Steven
Bast, Robert C.
Carson, Daniel D.
author_facet Morgado, Micaela
Sutton, Margie N.
Simmons, Mary
Warren, Curtis R.
Lu, Zhen
Constantinou, Pamela E.
Liu, Jinsong
Francis, Lewis LW.
Conlan, R. Steven
Bast, Robert C.
Carson, Daniel D.
author_sort Morgado, Micaela
collection PubMed
description 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.
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spelling pubmed-49247582016-07-13 Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB Morgado, Micaela Sutton, Margie N. Simmons, Mary Warren, Curtis R. Lu, Zhen Constantinou, Pamela E. Liu, Jinsong Francis, Lewis LW. Conlan, R. Steven Bast, Robert C. Carson, Daniel D. Oncotarget Research Paper 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. Impact Journals LLC 2016-02-24 /pmc/articles/PMC4924758/ /pubmed/26918940 http://dx.doi.org/10.18632/oncotarget.7652 Text en Copyright: © 2016 Morgado et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Morgado, Micaela
Sutton, Margie N.
Simmons, Mary
Warren, Curtis R.
Lu, Zhen
Constantinou, Pamela E.
Liu, Jinsong
Francis, Lewis LW.
Conlan, R. Steven
Bast, Robert C.
Carson, Daniel D.
Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title_full Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title_fullStr Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title_full_unstemmed Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title_short Tumor necrosis factor-α and interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB
title_sort tumor necrosis factor-α and interferon-γ stimulate muc16 (ca125) expression in breast, endometrial and ovarian cancers through nfκb
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924758/
https://www.ncbi.nlm.nih.gov/pubmed/26918940
http://dx.doi.org/10.18632/oncotarget.7652
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