GML sensitizes cancer cells to Taxol by induction of apoptosis.
Recently we identified a novel gene, gml, whose expression is regulated in a p53-dependent manner and found that gml expression was correlated with the sensitivity of esophageal cancer cells to anticancer drugs. To further investigate the biological mechanism of gml in determining the chemosensitivity of cancer cells to clinically useful agents, we introduced gml cDNA into TE10, an esophageal cancer cell line that lacks endogenous gml expression. In two resulting stable cell lines which expressed gml cDNA in the absence of wildtype p53, cell death occurred within 6 h after treatment with Taxol. TE10 parent cells or TE10 cells transfected with vector alone displayed relative resistance for 36 h. Induction of gml did not by itself affect viability. Morphological analysis confirmed that the increased chemosensitivity to Taxol conferred by gml was due to apoptosis. These data suggest that reduced expression of gml is likely to be associated with poor response rates to chemotherapy, and that an assay for gml expression might serve a clinical purpose as a predictor of chemotherapeutic sensitivity.
Kimura
Y
Y
Laboratory of Molecular Medicine, University of Tokyo.
Furuhata
T
T
Shiratsuchi
T
T
Nishimori
H
H
Hirata
K
K
Nakamura
Y
Y
Tokino
T
T
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics*; D009363:Neoplasm Proteins; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; C102519:GML protein, human; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D004318:Doxycycline; D017239:Paclitaxel