RGD Reference Report - Vitamin D receptor stable transfection restores the susceptibility to 1,25-dihydroxyvitamin D3 cytotoxicity in a rat glioma resistant clone. - Rat Genome Database

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Vitamin D receptor stable transfection restores the susceptibility to 1,25-dihydroxyvitamin D3 cytotoxicity in a rat glioma resistant clone.

Authors: Davoust, N  Wion, D  Chevalier, G  Garabedian, M  Brachet, P  Couez, D 
Citation: Davoust N, etal., J Neurosci Res 1998 Apr 15;52(2):210-9.
RGD ID: 70308
Pubmed: PMID:9579411   (View Abstract at PubMed)
DOI: DOI:10.1002/(SICI)1097-4547(19980415)52:2<210::AID-JNR9>3.0.CO;2-D   (Journal Full-text)

Recently, 1,25-dihydroxyvitamin D3 (1,25-D3) and less hypercalcemic analogs were shown to exert a delayed cytotoxic effect on rat C6 glioma cells. 1,25-D3 induces in these cells a programmed cell death, accompanied by the induction of c-myc, p53 and gadd 45 genes. The involvement of the intracellular vitamin D receptor (VDR) remained to be determined. In this lethal process, we have investigated its role in a subclone of C6 cells, which was isolated on the basis of its resistance to 1,25-D3, and in which VDR expression was not detected either at the mRNA or protein levels. The stable transfection of a rat VDR cDNA into this clone restored its susceptibility to the cytotoxic effects of 1,25-D3. This phenomenon was accompanied by a dramatic upregulation of c-myc mRNA expression, as already described in a C6-sensitive clone. These results provide the first evidence that VDR expression, if not sufficient, is necessary to mediate 1,25-D3 cytotoxic effect in C6 glioma cells. Since VDR mRNA expression has been already reported in human brain tumors, our data imply that the identification of VDR expression could become a prerequisite in any strategy of glioma treatment with vitamin D analogs.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
VdrRatapoptotic signaling pathway  IDA  RGD 
VdrRatregulation of transcription by RNA polymerase II  TAS  RGD 

Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
VdrRatnuclear receptor activity  IDA  RGD 


Genes (Rattus norvegicus)
Vdr  (vitamin D receptor)