Gene therapy for gastric cancer moves closer

Researchers have identified three promoter genes that upregulate the luciferase reporter gene with cytotoxic consequences, raising the possibility of a new approach to gastric cancer. In recent years, there have been numerous reports on gastric cancer-related genes but this knowledge has not yet been exploited for gene therapy approaches. An apt combination of a strong promoter with a suicide gene has already been suggested for melanoma cell lines.

Researchers have identified three promoter genes that upregulate the luciferase reporter gene with cytotoxic consequences, raising the possibility of a new approach to gastric cancer. In recent years, there have been numerous reports on gastric cancer-related genes but this knowledge has not yet been exploited for gene therapy approaches. An apt combination of a strong promoter with a suicide gene has already been suggested for melanoma cell lines. In the present study, Susanne Aberle (University of Tbingen, Germany) and colleagues monitored the transcriptional efficiency of a variety of genes known to be significantly expressed in gastric tumor cells, with the aim of selecting optimally active promoters for therapeutic recombinant DNA constructs. Using promoter-reporter gene (luciferase) constructs they compared the activities of KRT19, TFF1, SEL1L, MUC4, MUC1, CEL and hTERT by transfecting them into the gastrointestinal cell lines MKN45 and DAN-G. “The promoters of SEL1L, MUC1 and KRT19 displayed the highest activity levels in reporter gene assays,” they report in the European Journal of Gastroenterology and Hepatology. The team then tested the expression of the prokaryotic cytosine deaminase and its cytotoxic effects in cell cultures containing the three most active promoters. When driving cytosine deaminase in MKN45 cells, the SEL1L promoter induced a 66% cytotoxic effect and the TP1 promoter reached 82%, Aberle and coworkers report. They conclude: “Although this finding appears very promising, it evidently requires, next to additional in vitro studies, further confirmation in tumor transplants prior to any human experimentation.”(source Eur J Gastroenterol Hepatol 2003; 15: 1287-1292)