GML SENSITIZES CANCER-CELLS TO TAXOL BY INDUCTION OF APOPTOSIS

Recently we identified a novel gene, gml, whose expression is regulate d in a p53-dependent manner and found that gml expression was correlat ed with the sensitivity of esophageal cancer cells to anticancer drugs . To further investigate the biological mechanism of gml in determinin g the chemosensitivity of cancer cells to clinically useful agents, we introduced gml cDNA into TE10, an esophageal cancer cell line that la cks endogenous gml expression. In two resulting stable cell lines whic h expressed gml cDNA in the absence of wild-type p53, cell death occur red within 6 h after treatment with Taxol. TE10 parent cells or TE10 c ells transfected with vector alone displayed relative resistance for 3 6 h. Induction of gml did not by itself affect viability. Morphologica l analysis confirmed that the increased chemosensitivity to Taxol conf erred by gml was due to apoptosis. These data suggest that reduced exp ression of gml is likely to be associated with poor response rates to chemotherapy, and that an assay for gml expression might serve a clini cal purpose as a predictor of chemotherapeutic sensitivity.