FUNCTIONAL ANALYSIS OF REPRIMO AS A SUPPRESSOR GENE IN GASTRIC CANCER

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Abstract

Background

Reprimo was demonstrated to be a highly glycosylated protein, inducing cell cycle G2 arrest. Reprimo promoter methylation has been also reported as the mechanism regulating its expression in gastric cancer, but the biological roles largely remain unclear.

Methods

The methylation status of the Reprimo promoter was analyzed using quantitative methylation-specific polymerase chain reaction, and the effects of expression were examined using Reprimo stable transfection.

Results

Reprimo expression was induced by DNA damaging treatment in cell lines without its hypermethylation, but not those with its hypermethylation, in that Reprimo expression could be restored by treatment with a demethylating agent. Exogenous Reprimo expression significantly inhibited cell proliferation and colony formation and enhanced sensitivity to DNA damage, such as cisplatin or irradiation treatment.

Conclusion

Reprimo expression is inducible under DNA damaging agents, leading to decreased growth, but its expression is frequently suppressed by promoter methylation. Thus, Reprimo methylation status is considered to have a great potential as a predictive biomarker to select patients who may be effective for anticancer therapy in gastric cancer.

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