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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
VdrRatapoptotic signaling pathway  IDA  RGD 
VdrRatregulation of transcription by RNA polymerase II  TAS  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
VdrRatnuclear receptor activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vdr  (vitamin D receptor)


Additional Information