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Benzo[a]pyrene-induced cell cycle progression occurs via ERK-induced Chk1 pathway activation in human lung cancer cells.
- Source :
-
Mutation research [Mutat Res] 2015 Mar; Vol. 773, pp. 1-8. Date of Electronic Publication: 2015 Jan 28. - Publication Year :
- 2015
-
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 that activation of ERK and its downstream mediator Chk1 may contribute to B[a]P-induced S phase accumulation in H1355 cells. The results could help in the development of lung cancer treatments that target the Chk1 pathway through ERK.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Cell Cycle drug effects
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Checkpoint Kinase 1
Humans
Lung Neoplasms drug therapy
Signal Transduction drug effects
Benzo(a)pyrene pharmacology
Extracellular Signal-Regulated MAP Kinases physiology
Lung Neoplasms pathology
Protein Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-135X
- Volume :
- 773
- Database :
- MEDLINE
- Journal :
- Mutation research
- Publication Type :
- Academic Journal
- Accession number :
- 25769181
- Full Text :
- https://doi.org/10.1016/j.mrfmmm.2015.01.009