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Cell Growth & Differentiation Vol. 12, 319-326, June 2001
© 2001 American Association for Cancer Research

Transcriptional Regulation of the Vitamin D3 Receptor Gene by ZEB1

Darina L. Lazarova, Michael Bordonaro and Alan C. Sartorelli2

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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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2001 by the American Association of Cancer Research.