Cyclin A is essential for the p53-modulated inhibition from benzo(a)pyrene toxicity in A549 cells.
Benzo(a)pyrene (B(a)P) is an environment carcinogen that can enhance cell proliferation by disturbing the signal transduction pathways in cell cycle regulation. The p53 tumor suppressor as a cell cycle check-point determinant plays a critical role in cell proliferation. However, the mechanism of p53 that accounts for the remarkable toxicity of B(a)P remains elusive. Here we reported that exposure of B(a)P to A549 cells caused G1 to S and G2/M phase transition along with increased expression of p53, cyclin D1, Cdk2, Cdk4, p21 and decreased expression of cyclin E, but no change in cyclin A and p27 expression. Up-regulation of p53 expression via transfection caused G1 phase arrest with decreased expression of cyclin A, E, Cdk2 and Cdk4, and increased expression of p21, when the expression of cyclin D1 and p27 were not significant changed. While B(a)P exposure to A549 cells following p53 transfection, up-regulation of p53 significantly attenuated the B(a)P-induced enhancement of cell proliferation and cell arrest, with increased expression of cyclin D1, Cdk2 and Cdk4, and with declined expression of cyclin A, cyclin E and p21, and p27 were not significant changed. Compared to the untreated cells, cylin A expression reduced in p53-transfected cells and in the B(a)P-treated cells following p53 transfection, but showed no change in the only B(a)P-treated cells. These results indicated that cyclin A is regulated by p53, not by B(a)P, and it is essential in the p53-modulated inhibition from benzo(a)pyrene toxicity in A549 cells, cyclin E and p21 also as downstream genes of p53 involved it, which is p27-independent.
Wang
Zhiqin
Z
Department of Pharmacology and Toxicology, China Agricultural University, Beijing 100094, People's Republic of China.
Qi
Yitao
Y
Chen
Qian
Q
Yang
Di
D
Tang
Shusheng
S
Jin
Xi
X
Gao
Jie
J
Fu
Juanling
J
Zhou
Zongcan
Z
Wang
Jie
J
Xiao
Xilong
X
D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D019925:Cyclin A / Q000235:genetics / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D002273:Carcinogens; D019925:Cyclin A; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene