Source:http://linkedlifedata.com/resource/pubmed/id/10676663
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2000-2-28
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pubmed:abstractText |
A gene related to cell differentiation was identified by differential display as a candidate suppressor of metastases in colon cancer. This gene, with a full-length cDNA of 3 kb, is expressed in normal colon and primary colon cancer tissues and cell lines but not in their metastatic counterparts. A GenBank search found that it is identical to a recently cloned gene, differentiation-related gene-1 (Drg-1), isolated from differentiated HT-29 colon cancer cells. Stable transfection of the SW620 metastatic colon cancer cell line with Drg-1 cDNA induced morphological changes consistent with differentiation and up-regulated the expression of several colonic epithelial cell differentiation markers (alkaline phosphatase, carcinoembryonic antigen, and E-cadherin). Moreover, the expression of Drg-1 is controlled by several known cell differentiation reagents, such as ligands of peroxisome proliferator-activated receptor gamma (troglitazone and BRL46593) and of retinoid X receptor (LG268), and histone deacetylase inhibitors (trichostatin A, suberoylanilide hydroxamic acid, and tributyrin). A synergistic induction of Drg-1 expression was seen with the combination of tributyrin and a low dose of 5'-aza-2'-dexoycytidine (100 nM), an inhibitor of DNA methylation. Functional studies revealed that overexpression of Drg-1 in metastatic colon cancer cells reduced in vitro invasion through Matrigel and suppressed in vivo liver metastases in nude mice. We propose that Drg-1 suppresses colon cancer metastasis by inducing colon cancer cell differentiation and partially reversing the metastatic phenotype.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/N-myc downstream-regulated gene 1...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoid X Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
749-55
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10676663-Animals,
pubmed-meshheading:10676663-Cell Cycle Proteins,
pubmed-meshheading:10676663-Cell Differentiation,
pubmed-meshheading:10676663-Colonic Neoplasms,
pubmed-meshheading:10676663-DNA Methylation,
pubmed-meshheading:10676663-Down-Regulation,
pubmed-meshheading:10676663-Female,
pubmed-meshheading:10676663-Gene Expression Regulation,
pubmed-meshheading:10676663-Genes, Tumor Suppressor,
pubmed-meshheading:10676663-Humans,
pubmed-meshheading:10676663-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10676663-Mice,
pubmed-meshheading:10676663-Mice, Nude,
pubmed-meshheading:10676663-Neoplasm Invasiveness,
pubmed-meshheading:10676663-Neoplasm Metastasis,
pubmed-meshheading:10676663-Proteins,
pubmed-meshheading:10676663-RNA, Messenger,
pubmed-meshheading:10676663-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:10676663-Receptors, Retinoic Acid,
pubmed-meshheading:10676663-Retinoid X Receptors,
pubmed-meshheading:10676663-Transcription Factors,
pubmed-meshheading:10676663-Tumor Cells, Cultured
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pubmed:year |
2000
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pubmed:articleTitle |
Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer.
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pubmed:affiliation |
Division of Gastroenterology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, 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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