Benzo[a]pyrene-induced cell cycle progression occurs via ERK-induced Chk1 pathway activation in human lung cancer cells

Mutation Research
Bing-Yen WangJiunn-Liang Ko

Abstract

Benzo[a]pyrene (B[a]P) is a potent lung carcinogen derived from tobacco smoking and environmental contamination. This study aimed to investigate the signal transduction pathway responsible for B[a]P-induced non-small cell lung cancer (NSCLC) development. We exposed the human NSCLC cell lines Calu-1, CL3, H1299, CH27, H23, and H1355 to B[a]P and assessed cell cycle progression using flow cytometry. Expression of cell cycle mediators was measured using Western blot analyses and electrophoretic mobility shift assays (EMSAs). B[a]P exposure dramatically induced S-phase accumulation in H1355 cells. Phospho-p53 (Ser15 and Ser20), phospho-ERK, phospho-p38, and Bax were significantly increased in H1355 cells whereas phospho-Rb was decreased in these cells. In addition, B[a]P induced phosphorylation of checkpoint kinase-1 (Chk1) but not Chk2. EMSA experiments revealed a slower migrating band after c-Myc bound the E-box in response to B[a]P treatment, which was abolished upon the addition of the ERK inhibitor PD98059 in H1355 cells. Phospho-ERK inhibition and dominant negative mutant Chk1 expression reversed B[a]P-induced S phase accumulation and downregulated phospho-Chk1 and phospho-ERK expression. Taken together, these results suggest...Continue Reading

References

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Mar 31, 2004·Toxicology and Applied Pharmacology·Katerina ChramostováMiroslav Machala
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Citations

Jun 18, 2015·Frontiers in Microbiology·P S S Rao, Santosh Kumar
Apr 1, 2018·European Journal of Clinical Investigation·Christiana DemetriouPaolo Vineis
Apr 3, 2020·International Journal of Molecular Sciences·Seung-Cheol JeeJung-Suk Sung
Mar 14, 2021·Environmental Pollution·Francisco Carlos da Silva JuniorSilvia Regina Batistuzzo de Medeiros

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