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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2001-4-5
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pubmed:abstractText |
Beta-catenin acts as a transcriptional coactivator by forming a complex with T-cell factor/lymphoid enhancer factor (TCF/LEF) DNA-binding proteins. Aberrant transactivation of a certain set of target genes by beta-catenin and TCF4 complexes has been implicated in familial and sporadic colorectal tumorigenesis. A colorectal cancer cell line, DLD-1, becomes irregularly multilayered, when maintained confluent for 2-3 weeks, and forms numerous dome-like polypoid foci piled-up over the surface of cell sheets. By the use of a strict tetracycline-regulation system, we found that the continuous suppression of beta-catenin/TCF4-mediated gene transactivation by dominant-negative TCF4B (deltaN30) reduced these piled-up foci and restored a simple monolayer of polarized columnar cells resembling normal intestinal epithelium. The restoration of epithelial cell polarity was evident in two ways: (a) the formation of microvilli over the apical surface; and (b) the distribution of a tight junction protein, ZO-1, to the lateral plasma membrane. Retroviral expression of stabilized beta-catenin (deltaN89) induced the formation of similar piled-up foci in untransformed IEC6 intestinal epithelial cells. Sulindac, a nonsteroidal antiinflammatory drug effective against colorectal tumorigenesis in familial adenomatous polyposis syndrome, suppressed the formation of foci. The loss of epithelial cell polarity may be a critical cellular event driving beta-catenin/TCF4-mediated intestinal tumorigenesis.
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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/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Doxycycline,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulindac,
http://linkedlifedata.com/resource/pubmed/chemical/TCF Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/TCF7L2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tcf7l2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor 7-Like 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/zonula occludens-1 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2751-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11289158-Adenocarcinoma,
pubmed-meshheading:11289158-Amino Acid Sequence,
pubmed-meshheading:11289158-Animals,
pubmed-meshheading:11289158-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11289158-Cell Division,
pubmed-meshheading:11289158-Cell Membrane,
pubmed-meshheading:11289158-Cell Polarity,
pubmed-meshheading:11289158-Colorectal Neoplasms,
pubmed-meshheading:11289158-Cytoskeletal Proteins,
pubmed-meshheading:11289158-Doxycycline,
pubmed-meshheading:11289158-Epithelial Cells,
pubmed-meshheading:11289158-Genes, MDR,
pubmed-meshheading:11289158-Humans,
pubmed-meshheading:11289158-Intestinal Mucosa,
pubmed-meshheading:11289158-Membrane Proteins,
pubmed-meshheading:11289158-Molecular Sequence Data,
pubmed-meshheading:11289158-Phosphoproteins,
pubmed-meshheading:11289158-Rats,
pubmed-meshheading:11289158-Retroviridae,
pubmed-meshheading:11289158-Sulindac,
pubmed-meshheading:11289158-TCF Transcription Factors,
pubmed-meshheading:11289158-Trans-Activators,
pubmed-meshheading:11289158-Transcription Factor 7-Like 2 Protein,
pubmed-meshheading:11289158-Transcription Factors,
pubmed-meshheading:11289158-Transcriptional Activation,
pubmed-meshheading:11289158-Tumor Cells, Cultured,
pubmed-meshheading:11289158-beta Catenin
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pubmed:year |
2001
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pubmed:articleTitle |
Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation.
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pubmed:affiliation |
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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