Article

Human MUC1 carcinoma antigen regulates intracellular oxidant levels and the apoptotic response to oxidative stress.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Journal of Biological Chemistry (impact factor: 4.77). 10/2003; 278(37):35458-64. DOI:10.1074/jbc.M301987200 pp.35458-64
Source: PubMed

ABSTRACT The DF3/MUC1 transmembrane oncoprotein is aberrantly overexpressed by most human carcinomas. Certain insights are available regarding a role for MUC1 in intracellular signaling; however, no precise function has been ascribed to this molecule. The present results demonstrate that MUC1 expression is up-regulated by oxidative stress and that this response is mediated by activation of MUC1 gene transcription. A role for MUC1 in the oxidative stress response is supported by the demonstration that MUC1 expression is associated with attenuation of endogenous and H2O2-induced intracellular levels of reactive oxygen species (ROS). MUC1-dependent regulation of ROS is mediated at least in part by up-regulation of anti-oxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) expression. In concert with these findings, we show that the apoptotic response to oxidative stress is attenuated by a MUC1-dependent mechanism. These results support a model in which activation of MUC1 by oxidative stress provides a protective function against increased intracellular oxidant levels and ROS-induced apoptosis.

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Keywords

anti-oxidant enzyme
 
apoptotic response
 
attenuation
 
DF3/MUC1 transmembrane oncoprotein
 
glutathione peroxidase
 
H2O2-induced intracellular levels
 
human carcinomas
 
intracellular oxidant levels
 
MUC1 gene transcription
 
MUC1-dependent regulation
 
oxidative stress
 
oxidative stress response
 
precise function
 
present results
 
reactive oxygen species
 
results support
 
ROS
 
ROS-induced apoptosis
 
superoxide dismutase
 
up-regulation
 

Li Yin