Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Lan, K.H. et al.

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

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.[1]

References

Tumor-specific gene expression in carcinoembryonic antigen--producing gastric cancer cells using adenovirus vectors. Lan, K.H., Kanai, F., Shiratori, Y., Okabe, S., Yoshida, Y., Wakimoto, H., Hamada, H., Tanaka, T., Ohashi, M., Omata, M. Gastroenterology (1996) [Pubmed]

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