Human MUC1 carcinoma antigen regulates intracellular oxidant levels and the apoptotic response to oxidative stress.
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.
Yin
Li
L
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Li
Yongqing
Y
Ren
Jian
J
Kuwahara
Hiroaki
H
Kufe
Donald
D
D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001943:Breast Neoplasms; D003110:Colonic Neoplasms; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018396:Mucin-1 / Q000235:genetics / Q000502:physiology*; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018396:Mucin-1; D016877:Oxidants; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide