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

S-U Han1, T-H Kwak, K H Her

  • 1Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Oncogene
|July 27, 2007
PubMed

Insights

Transforming growth factor-beta (TGF-beta) signaling activates carcinoembryonic antigen (CEA) family members, specifically CEACAM5 and CEACAM6, in gastric cancer cells. This pathway is crucial for CEA expression, impacting cell adhesion and differentiation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The carcinoembryonic antigen (CEA) family comprises diverse glycoproteins involved in cell adhesion and differentiation.
  • Transforming growth factor-beta (TGF-beta) signaling is known to stimulate CEA secretion, but specific targets and mechanisms remain unclear.

Purpose of the Study:

  • To identify specific CEAs regulated by TGF-beta signaling.
  • To elucidate the mechanism underlying TGF-beta-induced CEA expression in gastric cancer.

Main Methods:

  • Analysis of CEA expression in nine human gastric cancer cell lines.
  • Investigating TGF-beta signaling restoration in unresponsive cell lines (SNU638, SNU484).
  • Assessing CEACAM5 and CEACAM6 promoter activity and in vivo expression in Smad3 null mice.

Main Results:

  • TGF-beta-responsive gastric cancer cells exhibited positive CEA expression.
  • Restoring TGF-beta signaling induced CEACAM5 and CEACAM6 expression and promoter activity.
  • CEA expression was reduced in Smad3 null mice, indicating Smad3's role.

Conclusions:

  • CEACAM5 and CEACAM6 are identified as major target genes of Smad3-mediated TGF-beta signaling.
  • TGF-beta signaling plays a significant role in regulating CEA expression in gastric cancer.

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