α4在化学致癌物诱导细胞转化中的作用

doi:10.3969/j.issn.1004-616x.2014.01.001

Carcinogenesis, Teratogenesis & Mutagenesis

Function of α4 in human cell transformation induced by chemical carcinogens

ZHANG Biao，ZHU Xiao-nian，MA Lu，CHEN Wen，CHEN Li-ping*

(Faculty of Preventive Medicine，School of Public Health，Sun-Yat Sen University，Guangzhou 510080，Guangdong , China)

Received:2013-10-21 Revised:2013-12-05 Online:2014-01-30 Published:2014-01-30
Contact: CHEN Li-ping，E-mail：chenliping_happy06@163.com

Abstract

Abstract:

OBJECTIVE: To investigate the role for α4 in cell transformation induced by chemical carcinogens. METHODS：Immunoblotting was performed to examine the expression of α4 in chemical-transformed cells and tumor cell lines. Stable cell lines L02R-α4 and L02R-SHα4 were generated by infecting L02R cells with retroviral vectors encoding α4 or lentiviral α4 shRNA，respectively. Cell proliferation and anchorage-independent cell growth were examined in these cells. Immunoblotting analysis was applied to measure the phosphorylation status of p70S6K1 and 4E-BP1，which were the key members of mTOR pathway in established cells and transformed cell models L02RT-AFB1，HepG2，and SMMC with or without rapamycin treatment. RESULTS：The protein expression of α4 in chemical-transformed cells and tumor cell lines increased by 1.9-5.9 fold compared with non-transformed cells. Immunoblotting results verified that L02R-α4 and L02R SHα4 cells were successfully established. Ectopic expression of α4 promoted cell growth and led to cell transformation. Notable increased phosphorylation levels of S6K1 (Thr389) and 4E-BP1 (Thr37/46) were observed in transformed cells where α4 was overexpressed. Upon rapamycin treatment， phosphorylation of p70S6K1 and 4E-BP1 declined significantly in all cells. Particularly，the effects were more profound in L02R-SHα4 cells. CONCLUSION：Overexpression of α4 promoted cell proliferation and induced cell transformation via activation of mTOR signaling pathway.

Key words: cell transformation, α4, mTOR pathway, protein phosphatase 2A

ZHANG Biao，ZHU Xiao-nian，MA Lu，CHEN Wen，CHEN Li-ping. Function of α4 in human cell transformation induced by chemical carcinogens [J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2014.01.001.

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Function of α4 in human cell transformation induced by chemical carcinogens

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