Identification and characterization of a response element in the EGFR promoter that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast cancer cells
| Autor: | Susan A. Chrysogelos, Kenneth R. McGaffin |
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| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic Sp1 Transcription Factor Response element DNA Footprinting Breast Neoplasms Biology Sodium Chloride Ligands Calcitriol receptor Endocrinology Calcitriol Vitamin D Response Element Cell Line Tumor Humans Epidermal growth factor receptor RNA Messenger RNA Neoplasm Binding site Promoter Regions Genetic Molecular Biology Psychological repression Binding Sites Base Sequence Chromosome Mapping DNA Neoplasm Ligand (biochemistry) Molecular biology VDRE ErbB Receptors biology.protein Mutagenesis Site-Directed Receptors Calcitriol Female Protein Binding |
| Zdroj: | Journal of molecular endocrinology. 35(1) |
| ISSN: | 0952-5041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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