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MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression.


ABSTRACT:

Background

MUC16 (CA125) is a large transmembrane mucin protein (> 200 kDa) aberrantly expressed in approximately 80% of human epithelial ovarian cancers (EOC). MUC16 expression in EOC cells is associated with increased tumorigenesis and inhibiton of genotoxic drug-induced apoptosis. However, the mechanism by which MUC16 mediates these effects is unknown. In the present study, we investigated the mechanisms by which MUC16 attenuates TRAIL-induced apoptosis.

Methods

MUC16 expression was down-regulated by stably expressing an anti-MUC16 single-chain antibody (scFv) targeted to the endoplasmic reticulum (ER), which prevents cell surface localization of MUC16 in OVCAR3 cells. We also generated a MUC16 C-terminal domain (MUC16CTD) construct that was stably expressed in MUC16 nega

SUBMITTER: Matte I 

PROVIDER: S-EPMC4234371 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature