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Molecular changes during arsenic‐induced cell transformation
Author(s) -
Li Guanwu,
Lee LaiSheung,
Li Muyao,
Tsao SaiWah,
Chiu JenFu
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22683
Subject(s) - arsenite , microbiology and biotechnology , oxidative stress , cell growth , mapk/erk pathway , signal transduction , cell , kinase , chemistry , reactive oxygen species , thioredoxin , extracellular , biology , protein kinase a , biochemistry , arsenic , organic chemistry
Arsenic and its derivatives are naturally occurring metalloid compounds widely distributed in the environment. Arsenics are known to cause cancers of the skin, liver, lung, kidney, and bladder. Although numerous carcinogenic pathways have been proposed, the exact molecular mechanisms remain to be delineated. To further characterize the role of oxidative stress in arsenite‐induced cell transformation via the reactive oxygen species (ROS)‐mediated Ras/Erk pathway, here we demonstrated arsenite‐induced rat lung epithelial cell (LEC) transformation, epithelial–mesenchymal transition, stimulation of the extracellular signal‐regulated kinase signaling pathway, and enhancement of cell proliferation. However, there was no evidence of activation of the phosphoinositide 3‐kinase/protein kinase B pathway in arsenite‐induced transformed LECs. Since ROS is involved in arsenite‐induced LEC cell transformation, Redox‐status regulatory proteins (Cu/Zn SOD and thioredoxin) and arsenite‐induced LEC cell transformation were significantly inhibited by concurrent treatment with the antioxidants. Our experimental results clearly demonstrated that induction of p‐ERK and cell proliferation by arsenite is mediated via oxidative stress, since antioxidants can inhibit arsenite‐induced cell transformation. J. Cell. Physiol. 226: 3225–3232, 2011. © 2011 Wiley Periodicals, Inc.