gms | German Medical Science

In this study the molecular role of the DICE1 gene (DDX26) on human chromosome 13q14 as a tumor suppressor gene in prostate carcinomas was determined. To address this issue, the promoter of the DICE1 gene was identified and investigated functionally. The functional analysis of the DNA sequence before the transcription start site of the DICE1 gene revealed a sequence of 800 bp that showed promoter activity in COS-7 cells. In cell lines of non-small cell lung carcinomas, a different methylation pattern of CpG sites in the region immediately before the DICE1 gene was identified. This methylation pattern correlates with down-regulation of the DICE1 expression in the analyzed cell lines. Methylation of CpG sites in DICE1 promoter was also noted in the prostate carcinoma cell lines LNCaP and DU-145, which showed reduced DICE1 mRNA expression. After treatment of these cell lines with 5-Azacytidin, an inhibitor of DNA methyltransferase, re-expression of the DICE1 gene was found. Allelic deletion analysis of primary prostate carcinomas identified a LOH in 5 of 10 informative cases (50%) using microsatellite marker D13S284 that co-localized with the DICE1 gene. In eight prostate carcinomas, DNA was investigated using the bisulfite method. In four of eight cases methylated cytosines were identified in 8 of 16 analyzed CpG sites. In summary, the DICE1 gene acts as a tumor suppressor gene in prostate carcinoma cells and fulfills Knudson’s “two-hit” theory.