The effects of over-expression and suppression of Cdc25A on the S-phase checkpoint induced by benzo(a)pyrene.
Our previous results have indicated that Cdc25A is involved in benzo(a)pyrene (BaP)-induced S-phase checkpoint in 16HBE cells and A549 cells. In this paper, we reported the changes of the downstream molecular pathway of Cdc25A and the effects of over-expression and suppression of Cdc25A on BaP-induced S-phase checkpoint. In the S-phase checkpoint induced by BaP the reduction of Cdc25A contributes to cyclin A inhibition. Over-expression of Cdc25A abrogated BaP-induced S-phase arrest in 16HBE cells and concomitantly the expression levels of Cdk2 and cyclin A were not obviously changed by BaP when compared with the control. Cdc25A down-regulation by RNA interference (RNAi) prolonged the S-phase arrest induced by BaP and decreased clearly the expression levels of cyclin A and cyclin E. Therefore, our results further demonstrated that Cdc25A was an effector in Chk1-Cdc25A-cyclin A/Cdk2 pathway of S-phase checkpoint elicited by the carcinogen BaP in 16HBE cells.
Yao
Biyun
B
Department of Toxicology, Health Science Center, Peking University, Beijing 100083, PR China.
Fu
Juanling
J
Hu
Entan
E
Qi
Yanmin
Y
Zhou
Zongcan
Z
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects*; D014162:Transfection; D020687:cdc25 Phosphatases / Q000187:drug effects / Q000378:metabolism*
D002274:Carcinogens, Environmental; D019925:Cyclin A; D019927:Cyclin E; D034741:RNA, Small Interfering; D001564:Benzo(a)pyrene; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases