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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
44
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pubmed:dateCreated |
2004-10-25
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pubmed:abstractText |
The MUC1 transforming protein is aberrantly overexpressed by most human carcinomas. Recent studies demonstrated that MUC1 confers a protective function against oxidative stress-induced apoptosis; however, the mechanisms responsible for this response are not known. The present work demonstrates that MUC1 regulates FKHRL1/FOXO3a, a member of the forkhead family of transcription factors that induces oxidant scavenging and DNA repair. We show that MUC1 attenuates activation of the phosphoinositide 3-kinase --> phospho-Akt/PKB pathway in HCT116 colon carcinoma cells and thereby decreases FOXO3a phosphorylation. MUC1 is expressed as an N-terminal ectodomain that is tethered to the cell surface by a C-terminal transmembrane subunit. The results demonstrate that the MUC1 cytoplasmic domain is sufficient to induce FOXO3a activation and attenuation of oxidative stress. We also demonstrate that stable down-regulation of endogenous MUC1 in ZR-75-1 breast cancer cells inactivates FOXO3a, increases intracellular oxidant levels, and sensitizes cells to H(2)O(2)-induced necrosis. These findings indicate that MUC1 regulates the FOXO3a signaling pathway in a survival response to oxidative stress.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/FOXO3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Mucin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45721-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15322085-Apoptosis,
pubmed-meshheading:15322085-DNA-Binding Proteins,
pubmed-meshheading:15322085-Forkhead Transcription Factors,
pubmed-meshheading:15322085-HCT116 Cells,
pubmed-meshheading:15322085-Humans,
pubmed-meshheading:15322085-Hydrogen Peroxide,
pubmed-meshheading:15322085-Mucin-1,
pubmed-meshheading:15322085-Oxidative Stress,
pubmed-meshheading:15322085-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15322085-Phosphorylation,
pubmed-meshheading:15322085-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15322085-Proto-Oncogene Proteins,
pubmed-meshheading:15322085-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15322085-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
MUC1 oncoprotein activates the FOXO3a transcription factor in a survival response to oxidative stress.
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pubmed:affiliation |
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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