Environmental and molecular mutagenesis
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Environ. Mol. Mutagen. · Mar 2011
Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts.
Human cadmium (Cd) exposure is associated with cancers of the lung and kidney. Using cDNA microarray analysis, we have recently reported that the expression of E2F1 is reduced by Cd in human lung fibroblasts, indicating the possibility of G1-phase arrest. To test this hypothesis, we investigated the effects of Cd on the cyclin-dependent kinase (CDK2) and retinoblastoma protein (Rb) regulatory pathways in WI38 human lung fibroblasts. ⋯ The level of Rb-E2F1 complexes was increased, and the translocation of E2F1 to the nucleus was decreased by Cd treatment. Consequently, the transcriptional activity of E2F1 and the expression of the E2F1 target genes were also decreased by Cd. These results clearly demonstrate that Cd-mediated G1 arrest in WI38 cells is associated with the suppression of Rb phosphorylation and with the inhibition of E2F1 transcriptional activity.