β-catenin involvement in arsenite-induced VEGF expression in neuroblastoma SH-SY5Y cells
Article first published online: 1 AUG 2012
Copyright © 2012 Wiley Periodicals, Inc.
How to Cite
Watcharasit, P., Suntararuks, S., Visitnonthachai, D., Thiantanawat, A. and Satayavivad, J. (2012), β-catenin involvement in arsenite-induced VEGF expression in neuroblastoma SH-SY5Y cells. Environ. Toxicol.. doi: 10.1002/tox.21794
- Article first published online: 1 AUG 2012
- Manuscript Accepted: 30 JUN 2012
- Manuscript Revised: 28 JUN 2012
- Manuscript Received: 21 APR 2012
- The Chulabhorn Research Institute and Center of Excellence on Environmental Health and Toxicology (EHT), Office of the Higher Education Commission, Thailand
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, 2012.