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Transcriptional Regulation of the Vitamin D₃ Receptor Gene by ZEB¹

Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520

The hormone 1,25-dihydroxyvitamin D₃ influences the growth and differentiation of a number of cell types. The functions of 1,25-dihydroxyvitamin D₃ are mediated through the vitamin D₃ receptor (VDR); therefore, an understanding of the regulation of VDR expression is important when considering the molecular mechanisms of differentiation induced by vitamin D₃ and its analogues. ZEB, a Krüppel-type transcription factor known to repress the transcription of several genes, binds to two sites within the VDR promoter and activates the transcription of this receptor in a cell-specific manner. Transfection of ZEB into SW620 colon carcinoma cells results in an up-regulation of the expression of endogenous VDR, confirming the role of ZEB in the transcriptional activation of the VDR gene. The expression of VDR is also induced by c-MYB; thus, ZEB and c-MYB may modulate the levels of VDR expression during differentiation in embryonal development, as well as in cancer cells.

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