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Benzo(a)pyrene-caused increased G(1)-S transition requires the activation of c-Jun through p53-dependent PI-3K/Akt/ERK pathway in human embryo lung fibroblasts.
Jiao-S; Liu-BC; Gao-A; Ye-M; Jia-XW; Zhang-FM; Liu-HF; Shi-XL; Huang-CS
Toxicol Lett 2008 May; 178(3):167-175
Benzo(a)pyrene (B(a)P) is a potent lung carcinogen mainly derived from tobacco smoking and environmental contamination, however, the molecular mechanisms by which it accelerates the cell cycle progression and induces the abnormal cell proliferation are still far away from understood. Our current analysis of human embryo lung fibroblasts (HELF) showed that B(a)P exposure was able to promote cell cycle G(1)-S phase transition. This effect was correlated with c-Jun activation because inhibition of c-Jun by its dominant negative mutant (TAM67) reversed B(a)P action on cell cycle with the down-regulation of expression of cyclin D1, pRb and E2F1. Further study found that overexpression of dominant negative mutants of, PI-3K or Akt, dramatically reduced B(a)P-induced the activation of c-Jun and extracellular signaling regulated kinase (ERK), but not c-Jun NH2 terminal kinase (JNK). Inhibition of p53 by either its inhibitor pifithrin-alpha or p53 siRNA markedly increased B(a)P-induced the activation of c-Jun, Akt and ERK in this context. Take together, our results indicate that c-Jun activation by p53-dependent PI-3K/Akt/ERK pathway is responsible for B(a)P-induced cell cycle alternations in human embryo lung fibroblasts.
Alveolar-cells; Pulmonary-congestion; Pulmonary-disorders; Pulmonary-system-disorders; Lung; Lung-burden; Lung-cells; Lung-disorders; Lung-irritants; Quartz-dust; Cell-biology; Cell-metabolism; Carcinogenesis; Carcinogenicity; Carcinogens; Environmental-exposure; Environmental-hazards; Humans
BC Liu, Chinese Center for Disease Control & Prevent, Institute for Occupational Health & Poison Control, 29 Nan Wei Rd, Beijing 100050, Peoples R China
Issue of Publication
Page last reviewed: September 2, 2020Content source: National Institute for Occupational Safety and Health Education and Information Division