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Chromium IV exposure, via Src/Ras signaling, promotes cell transformation
Author(s) -
Ganapathy Suthakar,
Li Ping,
Lafontant Jean,
Xiong Rui,
Yu Tianqi,
Zhang Guojun,
Chen Changyan
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22639
Subject(s) - intracellular , hexavalent chromium , biology , downregulation and upregulation , carcinogen , microbiology and biotechnology , apoptosis , signal transduction , cancer research , cell signaling , chromium , biochemistry , chemistry , organic chemistry , gene
Hexavalent chromium [Cr(VI)] is a well‐known environment carcinogen. The exposure of Cr(VI) through contaminated soil, air particles, and drinking water is a strong concern for the public health worldwide. While many studies have been done, it remains unclear which intracellular molecules transduce Cr(VI)‐mediated carcinogenic signaling in cells to promote cancer. In this study, we demonstrated that upon Cr(VI) treatment, the intracellular receptor src was activated, which further upregulated Ras activity, leading to the augmentation of ROS and onset of ER stress in human lung epithelial BEAS‐2B or keratinocytes. These cells were formed colonies in soft agar cultures following the persistent Cr(VI) treatment. Furthermore, anti‐apoptotic factor Bcl‐2 was upregulated and activated in the colonies. Thus, our study suggests that Cr(VI), though activating the src and Ras signaling axis, perturbs redox state and invokes ER stress for the establishment of carcinogenic actions in the cells. In this process, Bcl‐2 appears playing an important role. By uncovering these intracellular targets, our study may help developing novel strategies for better environmental protection, especially in areas contaminated or polluted by Cr(VI) as well as for effective cancer treatments.