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

Micaela Morgado, Margie N. Sutton, Mary Simmons, Curtis R. Warren, Zhen Lu, Pamela E. Constantinou, Jinsong Liu, Lewis L.W. Francis, R. Steven Conlan, Robert C. Bast, Daniel D. Carson

Research output: Contribution to journalArticle

26 Scopus citations

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 TNFa (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 TNFa 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 TNFa 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.

Original languageEnglish (US)
Pages (from-to)14871-14884
Number of pages14
JournalOncotarget
Volume7
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • CA125
  • Cancer
  • Cytokine
  • MUC16
  • NFκB

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Tumor necrosis factor-α and Interferon-γ stimulate MUC16 (CA125) expression in breast, endometrial and ovarian cancers through NFκB'. Together they form a unique fingerprint.

Cite this