Tumor-specific gene expression in carcinoembryonic antigen--producing gastric cancer cells using adenovirus vectors

Gastroenterology. 1996 Nov;111(5):1241-51. doi: 10.1053/gast.1996.v111.pm8898638.


Background & aims: An increase of carcinoembryonic antigen (CEA) expression is noted in about 40% of patients with gastric cancer. Adenovirus-mediated gene therapy using the CEA promoter was investigated as a way to specifically target human CEA-producing gastric tumors.

Methods: Recombinant adenovirus vectors carrying a CEA promoter linked to the lacZ gene (AdCEA lacZ) or the cytosine deaminase gene (AdCEA-CD) were constructed. After infection with these vectors, CEA-producing (MKN45 and MKN28) and non-CEA-producing (MKN1) gastric cancer cells were analyzed for transgene expression and sensitivity to 5-fluorocytosine.

Results: The lacZ gene was expressed selectively in CEA-producing AdCEA-lacZ-infected cells in vitro and in vivo. Transduction of the vector containing the CEA-regulated cytosine deaminase gene (AdCEA-CD) resulted in extraordinary sensitivity of MKN45 and MKN28 cells to 5-fluorocytosine. This effect was not observed in MKN1 cells. Moreover, AdCEA-CD-infected MKN45 cells showed a profound in vitro neighbor cell killing effect in the presence of 5-fluorocytosine. This effect was attributed to the diffusion of 5-fluorouracil, resulting from conversion of 5-fluorocytosine to 5-fluorouracil by the cytosine deaminase-expressing cells.

Conclusions: The results of this study suggest that use of a CEA promoter in an adenovirus vector could confer selective expression of the cytosine deaminase gene in CEA-producing gastric cancer cells, rendering the transduced cells susceptible to 5 fluorocytosine. This system may be useful in gene therapy that targets CEA-producing gastric carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Carcinoembryonic Antigen / biosynthesis
  • Carcinoembryonic Antigen / genetics*
  • Cytosine Deaminase
  • Flucytosine / metabolism
  • Fluorouracil / metabolism
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Nucleoside Deaminases / genetics*
  • Promoter Regions, Genetic
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / therapy*
  • Tumor Cells, Cultured


  • Carcinoembryonic Antigen
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase
  • Fluorouracil