Inhibition of benzo(a)pyrene-induced cell cycle progression by all-trans retinoic acid partly through cyclin D1/E2F-1 pathway in human embryo lung fibroblasts.
Benzo(a)pyrene [B(a)P] is a potent environmental carcinogen, which induces cell cycle changes. All-trans retinoic acid (ATRA) is a promising agent in prevention and treatment of human cancers. In the present study, we investigated the inhibition of B(a)P-induced cell cycle progression by ATRA in human embryo lung fibroblast (HELF). Our results showed that after treatment with B(a)P, the expression of cyclin D1 and E2F-1 were both increased significantly in HELF. There were almost no changes of CDK4 and E2F-4 expression by treatment with B(a)P. As expected, pretreatment with ATRA could efficiently decrease B(a)P-induced overexpression of cyclin D1 and E2F-1. In a further study, we stably transfected antisense cyclin D1 and antisense CDK4 plasmid into HELF. The inhibition of cyclin D1 expression and the inhibition of CDK4 expression significantly impaired the B(a)P-induced overexpression of E2F-1 respectively. Pretreatment with ATRA, cells expressing antisense cyclinD1 or antisense CDK4 showed a lesser decrease of B(a)P-induced overexpression of E2F-1 compared with similarly treated HELF. Furthermore, flow cytometry analysis showed that B(a)P promoted cell cycle progression from G(1) phase to S phase, while pretreatment with ATRA could inhibit B(a)P-induced cell cycle progression by an accumulation of cells in the G(1) phase. It was suggested that ATRA could block B(a)P-induced cell cycle promotion partly through the cyclin D1/E2F-1 pathway in HELF.
Jia
Xiaowei
X
National Institute of Occupation Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nan Wei Road, Beijing 100050, China.
Liu
Bingci
B
Shi
Xianglin
X
Gao
Ai
A
You
Baorong
B
Ye
Meng
M
Shen
Fuhai
F
Du
Hongju
H
D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000196:embryology; D016372:RNA, Antisense; D014212:Tretinoin / Q000494:pharmacology*
D050687:E2F1 Transcription Factor; D016372:RNA, Antisense; D019938:Cyclin D1; D001564:Benzo(a)pyrene; D014212:Tretinoin; D051358:Cyclin-Dependent Kinase 4