Tributyltin induces a G2/M cell cycle arrest in human amniotic cells via PP2A inhibition-mediated inactivation of the ERK1/2 cascades |
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| Affiliation: | 1. Department of Biochemistry, School of Medicine, Nantong University, 19 Qi Xiu Rode, 226001 Nantong, China;2. Department of Biosystem Engineering, College of Biosystem Engineering and Food Science, Zhejiang University, 388 Yu Hang Tang Road, 310058 Hangzhou, China;3. Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, 388 Yu Hang Tang Road, 310058 Hangzhou, China;1. Department of Biochemistry and Biotechnology, Precarpathian National University named after Vassyl Stefanyk, 57 Shevchenko Str., Ivano-Frankivsk 76025, Ukraine;2. Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada;1. Radiation Biotechnology Laboratory, Department of Radiation Biosciences, Institute of Nuclear and Allied Sciences, Delhi 110054, India;2. Department of Biochemistry, Faculty of Science, Jamia Hamdard, Delhi 110062, India;1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt;2. Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt;1. Department of Chemical and Biological Engineering, Yancheng Institute of Technology, Yancheng 224003, PR China;2. State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Nanjing 210046, Jiangsu, PR China |
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| 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. |
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| Keywords: | Tributyltin Cell cycle arrest PP2A Cdc25C Cdc2 ERK1/2 cascades |
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