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Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts.
Environ Mol Mutagen. 2011 Mar; 52(2):145-52.EM

Abstract

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. We demonstrate here that G1-phase accumulation was induced by Cd in WI38 (wild-type for p53 and Rb), but not in the SV40 large T antigen-transformed variant WI38-VA13 (p53- and Rb-defective). Cd-induced cell-cycle arrest was associated with a decrease in CDK2 protein and with increase in p21 expression and p53 phosphorylation. Cd treatment caused a distinct increase in the formation of p21-cyclin E-CDK2 complex, as revealed by immunoprecipitation. 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.

Authors+Show Affiliations

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20839231

Citation

Choi, You-Jin, et al. "Involvement of E2F1 Transcriptional Activity in Cadmium-induced Cell-cycle Arrest at G1 in Human Lung Fibroblasts." Environmental and Molecular Mutagenesis, vol. 52, no. 2, 2011, pp. 145-52.
Choi YJ, Yin HQ, Suh HR, et al. Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts. Environ Mol Mutagen. 2011;52(2):145-52.
Choi, Y. J., Yin, H. Q., Suh, H. R., Lee, Y. J., Park, S. R., & Lee, B. H. (2011). Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts. Environmental and Molecular Mutagenesis, 52(2), 145-52. https://doi.org/10.1002/em.20593
Choi YJ, et al. Involvement of E2F1 Transcriptional Activity in Cadmium-induced Cell-cycle Arrest at G1 in Human Lung Fibroblasts. Environ Mol Mutagen. 2011;52(2):145-52. PubMed PMID: 20839231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of E2F1 transcriptional activity in cadmium-induced cell-cycle arrest at G1 in human lung fibroblasts. AU - Choi,You-Jin, AU - Yin,Hu-Quan, AU - Suh,Hyo-Ryung, AU - Lee,Young-Ju, AU - Park,So-Ra, AU - Lee,Byung-Hoon, PY - 2010/9/15/entrez PY - 2010/9/15/pubmed PY - 2011/3/22/medline SP - 145 EP - 52 JF - Environmental and molecular mutagenesis JO - Environ Mol Mutagen VL - 52 IS - 2 N2 - 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. We demonstrate here that G1-phase accumulation was induced by Cd in WI38 (wild-type for p53 and Rb), but not in the SV40 large T antigen-transformed variant WI38-VA13 (p53- and Rb-defective). Cd-induced cell-cycle arrest was associated with a decrease in CDK2 protein and with increase in p21 expression and p53 phosphorylation. Cd treatment caused a distinct increase in the formation of p21-cyclin E-CDK2 complex, as revealed by immunoprecipitation. 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. SN - 1098-2280 UR - https://www.unboundmedicine.com/medline/citation/20839231/Involvement_of_E2F1_transcriptional_activity_in_cadmium_induced_cell_cycle_arrest_at_G1_in_human_lung_fibroblasts_ L2 - https://doi.org/10.1002/em.20593 DB - PRIME DP - Unbound Medicine ER -