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β‐catenin involvement in arsenite‐induced VEGF expression in neuroblastoma SH‐SY5Y cells
Author(s) -
Watcharasit Piyajit,
Suntararuks Sumitra,
Visitthachai Daranee,
Thiantanawat Apinya,
Satayavivad Jutamaad
Publication year - 2014
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.21794
Subject(s) - arsenite , protein kinase b , pi3k/akt/mtor pathway , catenin , sh sy5y , chemistry , cancer research , carcinogenesis , biology , microbiology and biotechnology , neuroblastoma , signal transduction , arsenic , cell culture , biochemistry , wnt signaling pathway , genetics , organic chemistry , gene
Arsenic is a widespread contaminant in the environment especially in drinking water. Although it is a known carcinogen in human, the mechanism by which arsenic induces carcinogenesis is not well understood. Among several effects of arsenic, it has been suggested that arsenic‐induced vascular endothelial growth factor (VEGF) expression plays a critical role in arsenic carcinogenesis. In the present study, we demonstrated that arsenite induced VEGF expression in neuroblastoma SH‐SY5Y cells without induction of HIF‐1α, a well‐known transcriptional activator for VEGF suggesting that arsenite‐induced VEGF expression in SH‐SY5Y cells may not require HIF‐1α activation. It has been reported that VEGF expression is regulated by multiple transcription factors including β‐catenin. We therefore investigated whether β‐catenin was involved in arsenite‐induced VEGF expression in SH‐SY5Y cells. Treatment of arsenite caused β‐catenin accumulation in the nucleus. Additionally, arsenite treatment decreased the activity of GSK3, an enzyme that phosphorylates and targets β‐catenin for degradation by proteasome, without activation of its upstream kinase, Akt. Inhibition of PI3K/Akt which negatively regulates GSK3 activity by LY294002 resulted in a decrease in arsenite‐mediated β‐catenin nuclear accumulation, and VEGF expression. These results suggested that β‐catenin plays a role in arsenite‐induced VEGF in SH‐SY5Y cells, and the induction of β‐catenin by arsenite is mediated by inhibition of GSK3 without activating its upstream kinase Akt. © © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 672–678, 2014.