DIFFERENTIALLY EXPRESSED GENES IN C6.9 GLIOMA-CELLS DURING VITAMIN-D-INDUCED CELL-DEATH PROGRAM

C6.9 rat glioma cells undergo a cell death program when exposed to 1,2 5-dihydroxyvitamin D3 (1,25-D3). As a global analytical approach, we h ave investigated gene expression in C6.9 engaged in this cell death pr ogram using differential screening of a rat brain cDNA library with pr obes derived from control and 1,25-D3-treated cells. Using this method ology we report the isolation of 61 differentially expressed cDNAs. Fo rty-seven cDNAs correspond to genes already characterized in rat cells or tissues. Seven cDNAs are homologous to yeast, mouse or human genes and seven are not related to known genes. Some of the characterized g enes have been reported to be differentially expressed following induc tion of programmed cell death. These include PMP22/gas3, MGP and beta- tubulin. For the first time, we also show a cell death program induced up-regulation of the c-myc associated primary response gene CRP, and of the proteasome RN3 subunit and TCTP/mortalin genes. Another interes ting feature of this 1,25-D3 induced-cell death program is the down re gulated expression of transcripts for the microtubule motor dynein hea vy chain/MAP 1C and of the calcium-binding S100 beta protein. Finally 15 upregulated cDNAs encode ribosomal proteins suggesting a possible i nvolvement of the translational apparatus in this cell program. Altern atively, these ribosomal protein genes could be up regulated in respon se to altered rates of cellular metabolism, as has been demonstrated f or most of the other isolated genes which encode proteins involved in metabolic pathways. Thus, this study presents to our knowledge the fir st characterization of genes which are differentially expressed during a cell death program induced by 1,25-D3. Therefore, this data provide s new information on the fundamental mechanisms which participate in t he antineoplastic effects of 1,25-D3 and on the machinery of a cell de ath program in a glioma cell line.