Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Identification and characterization of a response element in the EGFR promoter that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast cancer cells.

McGaffin KR, Chrysogelos SA

Vincent T Lombardi Cancer Center, Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA. krmcgaffin@aol.com

Reduction of epidermal growth factor receptor (EGFR) mRNA and protein by 1,25-dihydroxyvitamin D3 has been documented in MCF7, T47D, and BT549 breast cancer cells. In the present report, functional mapping of the EGFR promoter in BT549 cells has revealed a sequence of DNA between nucleotide positions -536 and -478 that resembles a consensus vitamin D response element (VDRE) and confers a vitamin D response upon both the homologous and a minimal heterologous promoter. In vitro footprinting and gel shift assays demonstrate the presence of an unidentified nuclear factor that is required for strong binding of the vitamin D receptor (VDR) to this putative VDRE. An Sp1 binding site was also identified in close proximity and shown to bind Sp1 from nuclear extract. Mutational analysis and functional studies using a minimal heterologous promoter provide evidence that the VDR in concert with an unknown nuclear partner mediates basal EGFR repression through displacement of Sp1 which is augmented in the presence of a ligand.

Published 9 August 2005 in J Mol Endocrinol, 35(1): 117-33.
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