Expression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells.
DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated with their transferase activity levels, whereas Mer- cells contained undetectable amounts of transferase mRNA. The mRNA levels were not induced in human cells by treatments that induce other DNA damage-inducible genes. These results demonstrate that in human cells the transferase gene is constitutively expressed, that its expression is related to activity levels, and that in Mer- tumor cells the expression of the transferase gene is probably blocked at the level of mRNA production.
Fornace
A J
AJ
Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Papathanasiou
M A
MA
Hollander
M C
MC
Yarosh
D B
DB
D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics*; D009369:Neoplasms; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014965:X-Rays
D012333:RNA, Messenger; D008769:Methylnitronitrosoguanidine; D008741:Methyl Methanesulfonate; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase