Up-regulation of cyclin D1 by JNK1/c-Jun is involved in tumorigenesis of human embryo lung fibroblast cells induced by a low concentration of arsenite

被引:20
|
作者
Li, Yuan [1 ,2 ]
Shen, Lu [1 ,2 ]
Xu, Hui [1 ,2 ]
Pang, Ying [1 ,2 ]
Xu, Yuan [1 ,2 ]
Ling, Min [1 ,2 ]
Zhou, Jianwei [2 ]
Wang, Xinru [2 ]
Liu, Qizhan [1 ,2 ]
机构
[1] Nanjing Med Univ, Dept Toxicol, Sch Publ Hlth, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Key Lab Modern Toxicol, Minist Educ, Sch Publ Hlth, Nanjing 210029, Jiangsu, Peoples R China
关键词
Arsenite; Cell cycle; Jun-N-terminal kinase 1; c-Jun; Cyclin D1; Neoplastic transformation; SIGNAL-TRANSDUCTION PATHWAY; BREAST-CANCER CELLS; C-JUN; HUMAN KERATINOCYTES; INDUCED APOPTOSIS; GASTRIC-CANCER; IN-UTERO; PROLIFERATION; EXPRESSION; JNK;
D O I
10.1016/j.toxlet.2011.06.024
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Inorganic arsenic, a ubiquitous environmental contaminant, is associated with an increased risk of cancer. There are several hypotheses regarding arsenic-induced carcinogenesis. The mechanism of action remains obscure, although hyper-proliferation of cells is involved. In the present study, the molecular mechanisms underlying the proliferation and malignant transformation of human embryo lung fibroblast (HELF) cells induced by a low concentration of arsenite were investigated. The results reveal that a low concentration of arsenite induces cell proliferation and promotes cell cycle transition from the G(1) to the S phase. Moreover, arsenite activates the JNK1/c-Jun signal pathway, but not JNK2, which up-regulates the expression of cyclin D1/CDK4 and phosphorylates the retinoblastoma (Rb) protein. Blocking of the iNK1/c-Jun signal pathway suppresses the increases of cyclin D1 expression and Rb phosphorylation, which attenuates cell proliferation, reduces the transition from the Cl to the S phase, and thereby inhibits the neoplastic transformation of HELF cells induced by a low concentration of arsenite. Thus, activation of the JNK1/c-Jun pathway up-regulates the expression of cyclin D1, which is involved in the tumorigenesis caused by a low concentration of arsenite. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:113 / 120
页数:8
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