Induction of the c-myc but not the cH-ras promoter by platinum compounds.
The recombinant plasmids p324, p330 and p323 carrying the aminoglycoside phosphotransferase (aph) gene and 5' flanking c-myc sequences linked to the reporter gene chloramphenicol acetyl-transferase (cat) were introduced into the mouse erythroleukaemic cell line F412B2TK- and stable transfectants resistant to geneticin G418 were obtained. The effects of cis-platin and two novel platinum compounds, D19466 (lobaplatin) and D17872, on c-myc promoter regions were studied using a large range of drug concentrations and correlated with cytotoxicity data. It was found that cis-platin and D19466 show a similar pattern of cytotoxicity and activation of c-myc promoter-driven cat gene expression with maximum effect (increased expression of 7.4- and 8.1-fold, respectively) at a concentration of 5 x 10(-5) M, while the less cytotoxic D17872 only slightly activates cat expression at the same concentration. However, when the F412B2TK- cell line was transfected with a plasmid carrying 5' flanking sequences of the c-Hras1 gene with promoter/enhancer function, linked to the cat reporter, no similar inductive effect was observed with any of the platinum drugs used. These data suggest that platinum compounds and possibly other DNA-damaging agents may specifically influence the expression of certain genes.
Eliopoulos
A G
AG
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Kerr
D J
DJ
Maurer
H R
HR
Hilgard
P
P
Spandidos
D A
DA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005029:Ethylenediamines / Q000494:pharmacology; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D014407:Tumor Cells, Cultured
D003503:Cyclobutanes; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; C068760:D 17872; C066228:lobaplatin; D002945:Cisplatin