Vitamin D3 receptor/Sp1 complex is required for the induction of p27Kip1 expression by vitamin D3

Abstract

1,25-dihydroxyvitamin D₃ (vitamin D₃) has been shown to upregulate p27^Kip1 expression via Sp1 and NF-Y binding sites in the p27^Kip1 promoter. However, whether vitamin D₃ receptor (VDR) involves in this process is unclear. In this study, we demonstrated that expression of VDR in SW620 cells, which exhibited low level of endogenous VDR, increased vitamin D₃-stimulated p27^Kip1 promoter activity. On the contrary, suppression of Sp1 expression by small interference RNA reduced the stimulation of p27^Kip1 promoter activity by vitamin D₃ in LNCaP cells. DNA affinity precipitation assay and chromatin immunoprecipitation assay showed that VDR bound to the p27^Kip1 promoter in vitro and in vivo. In addition, we also demonstrated that VDR interacted with Sp1 in vitro and in cells. Collectively, our results suggest that VDR is involved in the induction of p27^Kip1 by vitamin D₃ and may interact with Sp1 to modulate the expression of target genes that lack VDR response element (VDRE) in their promoters.