title: Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis.
abstract: Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant. BaP is a known carcinogen and can induce malignant transformation of rodent and human cells. Many evidences suggest that inhibitor of poly(ADP-ribose) glycohydrolase (PARG) is potent anticancer drug candidate. However, the effect of PARG on BaP carcinogenesis remains unclear. We explored this question in a PARG-deficient human bronchial epithelial cell line (shPARG cells) treated with various concentration of BaP for 15 weeks. Soft agar assay was used to examine BaP-induced cell malignancy of human bronchial epithelial cells and shPARG cells. Mechanistic investigations were used by 2D-DIGE and mass spectrometry. Western blot analysis and Double immunofluorescence detection were used to confirm some of the results obtained from DIGE experiments. We found that PARG silencing could dramatically inhibit BaP-induced cell malignancy of human bronchial epithelial cells in soft agar assay. Altered levels of expression induced by BaP were observed within shPARG cells for numerous proteins, including proteins required for cell mobility, stress response, DNA repair and cell proliferation pathways. Among these proteins, TCTP and Cofilin-1 involved in malignancy, were validated by western blot analysis and immunofluorescence assay. PARG inhibition contributed to down-regulation of TCTP and Cofilin-1. This is the first experimental demonstration of a link between PARG silencing and reduced cell migration after BaP exposure. We propose that PARG silencing might down-regulate TCTP and Cofilin-1 associated with metastasis in BaP carcinogenesis.
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Haiyan
authors: H
authors: Huang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Xuan
authors: X
authors: Li
authors: Department of Preventive Medicine, Gannan Medical College Jiangxi, China.
authors: Gonghua
authors: G
authors: Hu
authors: School of Public Health, Guangxi Medical University Guangxi, China.
authors: Xiyi
authors: X
authors: Li
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Zhixiong
authors: Z
authors: Zhuang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Jianjun
authors: J
authors: Liu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Desheng
authors: D
authors: Wu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Linqing
authors: L
authors: Yang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Xinyun
authors: X
authors: Xu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Xinfeng
authors: X
authors: Huang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Jianqing
authors: J
authors: Zhang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Wen-Xu
authors: WX
authors: Hong
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Jianhui
authors: J
authors: Yuan
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Wei
authors: W
authors: Gao
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention Guangdong, China.
authors: Yinpin
authors: Y
authors: Liu
keywords: DNA damage; benzo(a)pyrene; human bronchial epithelial cells (16HBE cells); poly(ADP-ribose) glycohydrolase; poly(ADP-ribosyl)ation
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