Transcriptional regulation of the vitamin D-3 receptor gene by ZEB

The hormone 1,25-dihydroxyvitamin D-3 influences the growth and differentia tion of a number of cell types. The functions of 1,25-dihydroxyvitamin D-3 are mediated through the vitamin D-3 receptor (VDR); therefore, an understa nding of the regulation of VDR expression is important when considering the molecular mechanisms of differentiation induced by vitamin D-3 and its ana logues. ZEE, a Kruppel-type transcription factor known to repress the trans cription of several genes, binds to two sites within the VDR promoter and a ctivates the transcription of this receptor in a cell-specific manner. Tran sfection of ZEE into SW620 colon carcinoma cells results in an up-regulatio n of the expression of endogenous VDR, confirming the role of ZEE in the tr anscriptional activation of the VDR gene. The expression of VDR is also ind uced by c-MYB; thus, ZEE and c-MYB may modulate the levels of VDR expressio n during differentiation in embryonal development, as well as in cancer cel ls.