Protein Phosphatase and TRAIL Receptor Genes as New Candidate Tumor Genes on Chromosome 8p in Prostate Cancer

Cancer Genomics - Proteomics

WOLFGANG A. SCHULZ⁴  ADRIAN ALEXA²  MIRKO MÜLLER⁴  MASANORI YAMANAKA⁴  MAX HORNSTEIN⁴  VOLKER JUNG³  MICHÈLE J. HOFFMANN⁴  JÖRG RAHNENFÜHRER¹ 

[1] nstitute for Statistics, University of Dortmund, Dortmund, Germanynstitute for Statistics, University of Dortmund, Dortmund, Germanynstitute for Statistics, University of Dortmund, Dortmund, Germany;ax-Planck Institute for Informatics, 66123 Saarbrückenax-Planck Institute for Informatics, 66123 Saarbrückenax-Planck Institute for Informatics, 66123 Saarbrücken;epartment of Urology, Medical University of the Saarland, Homburgepartment of Urology, Medical University of the Saarland, Homburgepartment of Urology, Medical University of the Saarland, Homburg;epartment of Urology, Heinrich Heine University, Düsseldorfepartment of Urology, Heinrich Heine University, Düsseldorfepartment of Urology, Heinrich Heine University, Düsseldorf

关键词: Tumor suppressor;    DNA methylation;    allelic imbalance;    expression microarray;    real-time RT-PCR;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Background: Allelic losses on chromosome 8p are common in prostate carcinoma, but it is not known exactly how they contribute to cancer development and progression. Materials and Methods: Expression of 12 genes located across chromosome 8p, including established tumor suppressor candidates (CSMD1, DLC1, NKX3.1), and others from a new microarray-based comparison was studied by quantitative RT-PCR in 45 M0 prostate carcinomas and 13 benign prostate tissues. Results: Significantly reduced expression was observed for two protein phosphatase subunit genes (PPP2CB, PPP3CC) and two TRAIL decoy receptors (TNFRSF10C/DcR1, TNFRSF10D/DcR2), but not for the three established candidates nor for TRAIL death receptor genes. Low expression of PPP3CC and TNFRSF10C located at 8p21.3 was highly significantly associated with tumor recurrence. In addition to allele loss, down-regulation of TNFRSF10C and TNFRSF10D was found to be associated with hypermethylation, although bisulfite sequencing usually revealed it to be partial. Conclusion: Our data strongly support a recent proposal that a segment at 8p21.3 contains crucial prostate cancer tumor suppressors. In addition, they raise the paradoxical issue of why TRAIL decoy receptors rather than death receptors are down-regulated in aggressive prostate cancer.

【 授权许可】

Unknown