CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling

S. U. Han, T. H. Kwak, K. H. Her, Y. H. Cho, Chul Won Choi, H. J. Lee, S. Hong, Y. S. Park, Y. S. Kim, T. A. Kim, S. J. Kim

Research output: Contribution to journalArticle

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Abstract

The carcinoembryonic antigen (CEAs) family consists of a large group of evolutionarily and structurally divergent glycoproteins. The transforming growth factor-β (TGF-β) signaling pathway has been implicated in the stimulation of CEA secretion in TGF-β-sensitive colon cells, thereby possibly modulating cell adhesion and differentiation. However, the specific CEAs targeted by TGF-β 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-β signaling pathway. In nine human gastric cancer cell lines examined, TGF-β-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-β signaling in CEA expression, we selected two TGF-β unresponsive gastric cancer cell lines; SNU638 cells that contain a mutation in the TGF-β type II receptor and SNU484 cells that express low to undetectable level of the TGF-β pathway intermediate protein, Smad3. Restoration of TGF-β 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-β signaling.

Original languageEnglish
Pages (from-to)675-683
Number of pages9
JournalOncogene
Volume27
Issue number5
DOIs
Publication statusPublished - 2008 Jan 24
Externally publishedYes

Fingerprint

Carcinoembryonic Antigen
Transforming Growth Factors
Genes
Cell Line
Stomach Neoplasms
Smad3 Protein
Growth Factor Receptors
Cell Adhesion
Cell Differentiation
Stomach
Glycoproteins
Colon
Epithelium

Keywords

  • Carcinoembryonic antigen
  • Gastric cancer
  • Smad3
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Han, S. U., Kwak, T. H., Her, K. H., Cho, Y. H., Choi, C. W., Lee, H. J., ... Kim, S. J. (2008). CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling. Oncogene, 27(5), 675-683. https://doi.org/10.1038/sj.onc.1210686

CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling. / Han, S. U.; Kwak, T. H.; Her, K. H.; Cho, Y. H.; Choi, Chul Won; Lee, H. J.; Hong, S.; Park, Y. S.; Kim, Y. S.; Kim, T. A.; Kim, S. J.

In: Oncogene, Vol. 27, No. 5, 24.01.2008, p. 675-683.

Research output: Contribution to journalArticle

Han, SU, Kwak, TH, Her, KH, Cho, YH, Choi, CW, Lee, HJ, Hong, S, Park, YS, Kim, YS, Kim, TA & Kim, SJ 2008, 'CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling', Oncogene, vol. 27, no. 5, pp. 675-683. https://doi.org/10.1038/sj.onc.1210686
Han, S. U. ; Kwak, T. H. ; Her, K. H. ; Cho, Y. H. ; Choi, Chul Won ; Lee, H. J. ; Hong, S. ; Park, Y. S. ; Kim, Y. S. ; Kim, T. A. ; Kim, S. J. / CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-β signaling. In: Oncogene. 2008 ; Vol. 27, No. 5. pp. 675-683.
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