Transcriptional regulation of the vitamin D(3) receptor gene by ZEB.
The hormone 1,25-dihydroxyvitamin D(3) influences the growth and differentiation 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 understanding of the regulation of VDR expression is important when considering the molecular mechanisms of differentiation induced by vitamin D(3) 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.
Lazarova
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Department of Pharmacology and Developmental Therapeutics Program, Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Bordonaro
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Sartorelli
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D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D018398:Homeodomain Proteins; D020598:Proto-Oncogene Proteins c-myb; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; D014157:Transcription Factors