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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-1-24
pubmed:abstractText
The carcinoembryonic antigen (CEAs) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The transforming growth factor-beta (TGF-beta) signaling pathway has been implicated in the stimulation of CEA secretion in TGF-beta-sensitive colon cells, thereby possibly modulating cell adhesion and differentiation. However, the specific CEAs targeted by TGF-beta signaling or underlying mechanism of the expression of CEAs has not yet been clarified. In this study, we investigated the specific CEAs targeted by the TGF-beta signaling pathway. In nine human gastric cancer cell lines examined, TGF-beta-responsive cell lines showed positive expression of CEAs. Expression patterns of CEA proteins correlated well with the level of CEA (CEACAM5) and CEACAM6 transcripts in these cell lines, but CEACAM1 expression was not observed in all of these cells. To investigate the role of TGF-beta signaling in CEA expression, we selected two TGF-beta unresponsive gastric cancer cell lines; SNU638 cells that contain a mutation in the TGF-beta type II receptor and SNU484 cells that express low to undetectable level of the TGF-beta pathway intermediate protein, Smad3. Restoration of TGF-beta signaling in these cells induced expression of the CEAs and increased activity of both CEA (CEACAM5) and CEACAM6 promoters. CEA expression was observed in the epithelium of the stomach of wild-type mice, but was markedly decreased in Smad3 null mice. These findings suggest that CEA (CEACAM5) and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/CD66 antigens, http://linkedlifedata.com/resource/pubmed/chemical/CEACAM6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules, http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth..., http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
675-83
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-beta signaling.
pubmed:affiliation
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural