DEXAMETHASONE SUPPRESSES APOPTOSIS IN A HUMAN GASTRIC-CANCER CELL-LINE THROUGH MODULATION OF BCL-X GENE-EXPRESSION

Treatment of human gastric cancer TMK-1 cells with transcription and t ranslation inhibitors rapidly triggered cell apoptosis, Along with cel l apoptosis, the Bcl-x(S) level was markedly upregulated suggesting a crucial role of this protein in promoting the apoptotic process. In th e presence of dexamethasone, however, cell apoptosis was greatly atten uated as demonstrated by DNA histogram shift and DNA fragmentation. St udies using the glucocorticoid receptor antagonist RU486 indicated tha t attenuation of apoptosis was mediated through glucocorticoid recepto rs, Dexamethasone not only suppressed the apoptosis-associated upregul ation of Bcl-x(S) but also enhanced the basal level of Bcl-x(L) in the cells. In addition, bcl-x mRNA stability was significantly extended i n the presence of dexamethasone. These results indicate that dexametha sone exerted a protective effect and delayed apoptosis of TMK-1 cells by modulating bcl-x gene expression. (C) 1997 Federation of European B iochemical Societies.