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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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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. |
format | Online Article Text |
id | pubmed-4924758 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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