Induction of the c-myc but not the cH-ras promoter by platinum compounds
| Autor: | Demetrios A. Spandidos, David J. Kerr, Peter Hilgard, H. Rainer Maurer, Aristides G. Eliopoulos |
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| Rok vydání: | 1995 |
| Předmět: |
Organoplatinum Compounds
Genes myc Biology Biochemistry Mice Plasmid Gene expression Tumor Cells Cultured Animals Humans Enhancer Promoter Regions Genetic Gene Pharmacology Reporter gene Dose-Response Relationship Drug Transfection Ethylenediamines Molecular biology Rats Lobaplatin Genes ras Cell culture Cisplatin Cell Division Cyclobutanes |
| Zdroj: | Biochemical pharmacology. 50(1) |
| ISSN: | 0006-2952 |
| Popis: | 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 × 10−5M, 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. |
| Databáze: | OpenAIRE |
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