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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-28
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
749-55
pubmed:dateRevised
2007-11-14
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
pubmed:year
2000
pubmed:articleTitle
Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer.
pubmed:affiliation
Division of Gastroenterology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.