Functionality of unliganded VDR in breast cancer cells: Repressive action on CYP24 basal transcription

Fatouma Alimirah, Avani Vaishnav, Michael McCormick, Ibtissam Echchgadda, Bandana Chatterjee, Rajendra G. Mehta, Xinjian Peng

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

It is well-established that CYP24, an immediate target gene of VDR is upregulated by VDR ligands. This study is focused on the functional role of unliganded VDR by investigating the correlation between the expression of VDR protein and basal mRNA levels of CYP24 in breast cancer cell lines. Analyses of multiple breast cancer cell lines demonstrated an inverse correlation between VDR protein expression and CYP24 mRNA expression levels; while in the presence of ligand, VDR protein level was positively correlated with CYP24 expression. In MCF-7 cells, VDR was mainly distributed in the nuclei in the absence of ligand. VDR overexpression in MCF-7 cells and MDA-MB231 cells decreased CYP24 mRNA expression levels and CYP24 promoter activity. Conversely, knock-down of VDR using siRNA techniques in MCF-7 and T47D cells significantly increased CYP24 mRNA expression. We also found that overexpression of VDR with a polymorphic site (FokI-FF) at its AF-1 domain, which makes VDR shorter by three amino acids, failed to repress CYP24 promoter activity. This report provides conclusive evidence for the repressive action of unliganded VDR on the expression of its target gene CYP24 and the importance of an intact VDR AF-1 domain for its repressive action.

Original languageEnglish (US)
Pages (from-to)143-150
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume342
Issue number1-2
DOIs
StatePublished - Sep 2010

Keywords

  • Breast cancer cells
  • CYP24
  • Unliganded VDR
  • Vitamin D receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Functionality of unliganded VDR in breast cancer cells: Repressive action on CYP24 basal transcription'. Together they form a unique fingerprint.

Cite this