title: Tributyltin induces a G2/M cell cycle arrest in human amniotic cells via PP2A inhibition-mediated inactivation of the ERK1/2 cascades.
abstract: The molecular mechanisms underlying the cell cycle alterations induced by tributyltin (TBT), a highly toxic environmental contaminant, remain elusive. In this study, cell cycle progression and some key regulators in G2/M phase were investigated in human amniotic cells treated with TBT. Furthermore, protein phosphatase (PP) 2A and the ERK cascades were examined. The results showed that TBT caused a G2/M cell cycle arrest that was accompanied by a decrease in the total cdc25C protein level and an increase in the p-cdc2 level in the nucleus. TBT caused a decrease in PP2A activity and inhibited the ERK cascade by inactivating Raf-1, resulting in the dephosphorylation of MEK1/2, ERK1/2, and c-Myc. Taken together, TBT leads to a G2/M cell cycle arrest in FL cells, an increase in p-cdc2 and a decrease in the levels of total cdc25C protein, which may be caused by the PP2A inhibition-mediated inactivation of the ERK1/2 cascades.
authors.affiliation: Department of Biochemistry, School of Medicine, Nantong University, 19 Qi Xiu Rode, 226001 Nantong, China; Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, 388 Yu Hang Tang Road, 310058 Hangzhou, China. Electronic address: zyl031912@163.com.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biosystem Engineering, College of Biosystem Engineering and Food Science, Zhejiang University, 388 Yu Hang Tang Road, 310058 Hangzhou, China. Electronic address: guozonglou@zju.edu.cn.
authors.forename: Zonglou
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, 388 Yu Hang Tang Road, 310058 Hangzhou, China. Electronic address: xulihong@zju.edu.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Xu
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004785:Environmental Pollutants / Q000633:toxicity*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D014220:Trialkyltin Compounds; C011559:tributyltin; D011494:Protein Kinases; D054648:Protein Phosphatase 2; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases
keywords: Cdc2; Cdc25C; Cell cycle arrest; ERK1/2 cascades; PP2A; Tributyltin