1α,25OH2D3 down-regulates HBp17/FGFBP-1 expression via NF-κB pathway

Abstract

The heparin binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1, GenBank accession no. NP-005121) has been reported to enhance angiogenesis as well as promotes tumor growth in vivo. Furthermore, this molecule was found to be highly expressed in the tissue and cell lines of oral squamous cell carcinoma (OSCC). 1α,25(OH)2D3 is used to study its potential to curb the expression of HBp17/FGFBP-1 in cancer cells. Consequently, we found that HBp17/FGFBP-1 mRNA and protein levels were significantly down-regulated. In this present study, we show that this event takes place via the NF-κB pathway since mRNA and protein levels of this pathway regulator, IκBα, were found to be significantly up-regulated. Furthermore, the promoter activity of HBp17/FGFBP-1 (region between -217 and +61) measured by a luciferase reporter assay was down-regulated following treatment. Silencing of VDR with siRNA showed the effect of 1α,25(OH)2D3 on HBp17/FGFBP-1. Based on these findings, we concluded that 1α,25(OH)2D3 down-regulated HBp17/FGFBP-1 expression via NF-κB. This article is part of a Special Issue entitled 'Vitamin D Workshop'.