Different mechanisms are responsible for c-jun mRNA induction by cisplatin and ultraviolet light
| Autor: | Y B, Rabo, M C, Shoshan, S, Linder, J, Hansson |
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| Rok vydání: | 1996 |
| Předmět: |
Ultraviolet Rays
Lactams Macrocyclic Quinones Protein Serine-Threonine Kinases Protein-Tyrosine Kinases Enzyme Activation Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-raf Transcription Factor AP-1 Genes jun Rifabutin Proto-Oncogene Proteins Calcium-Calmodulin-Dependent Protein Kinases Benzoquinones Tumor Cells Cultured Humans RNA Messenger Cisplatin Enzyme Inhibitors Promoter Regions Genetic Melanoma HeLa Cells |
| Zdroj: | International journal of cancer. 65(6) |
| ISSN: | 0020-7136 |
| Popis: | Ultraviolet light (UV) and different DNA-damaging agents are known to induce AP-l-transcription-factor activity. Whereas UV induction appears to be triggered by events at the cell membrane, the mechanism of AP-l activation by alkylating or platinating agents is not known. We have here examined the effect of cisplatin on AP-l activity in RPMI-8322 melanoma cells. Cisplatin was found to induce binding of nuclear proteins to TRE elements from the c-jun and collagenase-gene promoters, and was also found to induce activation of a c-jun-promoter reporter construct. Compared with stimulation by UV, cisplatin stimulation of c-jun-promoter activity was found to be less sensitive to a dominant negative mutant of Raf-I protein kinase. Furthermore, whereas UV treatment resulted in strong MAP-kinase activation, cisplatin treatment resulted only in a weak and transient increase. These data suggest that the Raf-MAPK pathway is of minor importance for the induction of c-jun-promoter activity by cisplatin. Finally, we report that cisplatin induction of c-jun in RPMI-8322 cells was blocked by herbimycin A, an inhibitor of Src-family tyrosine kinases. In contrast, UV induction of c-jun was not blocked by herbimycin A. In conclusion, our data strongly suggest that UV and cisplatin induction of c-jun mRNA in RPMI-8322 melanoma cells occur by distinct mechanisms. |
| Databáze: | OpenAIRE |
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