engleski

Expression of the urokinase plasminogen activator gene by alkylation damage in glioblastoma cells

We have produced A8 and A4 transformants, expressing ada gene, bacterial analogue of the DNA methyltransferase, in A1235 human glioblastoma Mer- cells. Transformants were much more resistant to the citotoxic effect of MNNG and produced 3.7 and 3.4 times lower extracellular proteolytic activity, respectively, compared to A1235 cells. Here, the expression of the upa gene has been investigated in A1235 and A8 cells after exposure to 5 M MNNG. upa expression was not affected until 12 hours after exposure in both cell types. In A1235 cells 24 hours after exposure, the level of upa transcripts was 4 times higher, and after 48 and 72 hours 6.2 times higher than in controls. In A8 cells, 24, 48 and 72 hours after exposure we measured 2 times higher level of upa mRNA than in control, but 3 times lower than in A1235 cells. 24 hours after exposure, upa induction was not affected by cycloheximide added together with MNNG. The results demonstrate up regulation of urokinase in human glioblastoma Mer- cells after MNNG treatment. Induction of upa gene might therefore be cellular response to DNA damage.

ada-alkB operon; Mer phenotype; O6-methylguanine-DNA methyltransferase; plasminogen activator

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