Constitutive activation of epidermal growth factor receptor promotes tumorigenesis of Cr(VI)-transformed cells through decreased reactive oxygen species and apoptosis resistance development

Donghern Kim1, Jin Dai1, Leonard Yenwong Fai1, Hua Yao2, Young-Ok Son3, Lei Wang3, Poyil Pratheeshkumar3, Kazuya Kondo4, Xianglin Shi3, Zhuo Zhang1*

1 Graduate Center for Toxicology,

3 Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536, USA;

2 Department of Stomatology, First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, China;

4 Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8509, Japan.

Background: Chronic exposure to Cr(VI) causes cell transformation.

Results: Cr(VI)-transformed cells exhibit activated EGFR, reduced ROS generation, and development of apoptosis resistance.

Conclusion: Constitutive activation of EGFR promotes tumorigenesis of Cr(VI)-transformed cells.

Significance: Our findings provide a new understanding on carcinogenic mechanisms of not only Cr(VI) but also other metals, such as arsenic and nickel. It also can be used to formulate cancer prevention strategies.

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