Linked Life Data

12947088

Source:http://linkedlifedata.com/resource/pubmed/id/12947088

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2003-11-3
pubmed:abstractText
CDX2 is a caudal-related homeobox transcription factor whose expression in the adult is normally restricted to intestinal epithelium. Mice heterozygous for germ line Cdx2 inactivation develop intestinal polyps, and the lesions lack Cdx2 expression. Prior studies indicate some human colon carcinomas also lack CDX2 expression. To address the role of CDX2 defects in colon cancer development, we analyzed CDX2 expression in 45 primary colorectal carcinomas. Four carcinomas lacked CDX2 expression, and three others showed aberrant cytoplasmic localization of CDX2, although no significant CDX2 gene defects were seen in the seven tumors. Marked reductions in CDX2 transcript and protein levels were seen in five of 13 colorectal cell lines, and nuclear run-off data indicated reduced transcription was a major factor in CDX2 silencing. Treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A did not restore CDX2 expression in CDX2-negative lines. However, consistent with a role for dominant repression mechanisms in CDX2 silencing, all somatic cell hybrids resulting from pairwise fusions between colon cancer lines with intact CDX2 expression and lines lacking CDX2 had reduced CDX2 transcripts and protein. A roughly 9.5-kb 5'-flanking region from the human CDX2 gene contained key cis elements for regulating transcription in colon cancer cells. Restoration of CDX2 expression suppressed proliferation and soft agar growth in the CDX2-negative HT-29 colon cancer cell line. Our findings suggest CDX2 inactivation in colon cancer results from defects in trans-acting pathways regulating CDX2 transcription, and CDX2 silencing contributes to the altered phenotype of some colorectal cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44608-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12947088-Adenoma, pubmed-meshheading:12947088-Azacitidine, pubmed-meshheading:12947088-Blotting, Western, pubmed-meshheading:12947088-Cell Division, pubmed-meshheading:12947088-Colonic Neoplasms, pubmed-meshheading:12947088-Cytoplasm, pubmed-meshheading:12947088-DNA Methylation, pubmed-meshheading:12947088-Enzyme Inhibitors, pubmed-meshheading:12947088-Gene Expression, pubmed-meshheading:12947088-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12947088-Gene Silencing, pubmed-meshheading:12947088-Histone Deacetylase Inhibitors, pubmed-meshheading:12947088-Homeodomain Proteins, pubmed-meshheading:12947088-Humans, pubmed-meshheading:12947088-Hydroxamic Acids, pubmed-meshheading:12947088-Immunohistochemistry, pubmed-meshheading:12947088-Methyltransferases, pubmed-meshheading:12947088-Mutation, pubmed-meshheading:12947088-Mutation, Missense, pubmed-meshheading:12947088-Phenotype, pubmed-meshheading:12947088-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12947088-Rectal Neoplasms, pubmed-meshheading:12947088-Trans-Activators, pubmed-meshheading:12947088-Transcription, Genetic
pubmed:year
2003
pubmed:articleTitle
Silencing of CDX2 expression in colon cancer via a dominant repression pathway.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0638, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.