Induction of c-fos proto-oncogene in mesangial cells by cadmium.

The Journal of Biological Chemistry
Z Wang, D M Templeton

Abstract

Cadmium is mitogenic under some circumstances and has been shown to cause accumulation of transcripts for several proto-oncogenes in a variety of cells, but the mechanism(s) remain to be delineated. Here we show that CdCl2 causes an increase in c-fos mRNA within 30 min of exposure of mesangial cells. At 10 microM Cd2+, this increase persists for at least 8 h in both rat and human cells. The half-life of c-fos mRNA is the same whether it accumulates following 4 h of treatment with Cd2+ or is induced transiently by phorbol ester. Cycloheximide, which stabilizes the transcript, causes a synergistic increase when administered with CdCl2. Nuclear run-on analysis confirms that Cd2+ causes transcriptional activation of the c-fos gene. Calmodulin and Ca2+/calmodulin-dependent kinase, and classical protein kinase C (PKC) isoforms represent two Ca2+-dependent signaling pathways that can lead to induction of c-fos, and Cd2+ has been shown to activate both calmodulin and PKC in vitro, possibly by virtue of the similar ionic radii of Cd2+ and Ca2+. Therefore, we investigated the effect of Cd2+ on these pathways in vivo. 10 microM CdCl2 did not increase total PKC activity or Ca2+/calmodulin-dependent kinase II activity and inhibited the latt...Continue Reading

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