Different mechanisms are responsible for c-jun mRNA induction by cisplatin and ultraviolet light
✍ Scribed by Ylva Bendix Rabo; Maria C. Shoshan; Stig Linder; Johan Hansson
- Book ID
- 102651208
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 809 KB
- Volume
- 65
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Ultraviolet light (UV) and different DNA-damaging agents are known to induce AP-I -transcription-factor activity. Whereas UV induction appears to be triggered by events at the cell membrane, the mechanism of AP-I activation by alkylating or platinating agents is not known. We have here examined the effect of cisplatin on AP-I activity in RPMI-8322 melanoma cells. Cisplatin was found to induce binding of nuclear proteins to TRE elements from the c-jun and collagenare-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-junpromoter 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 mec hanisms.