Protein phosphatase and TRAIL receptor genes as new candidate tumor genes on chromosome 8p in prostate cancer.
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.


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.


CONCLUSIONS
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.
Hornstein
Max
M
Department of Urology, Heinrich Heine University, Dusseldorf, Germany.
Hoffmann
Michèle J
MJ
Alexa
Adrian
A
Yamanaka
Masanori
M
Müller
Mirko
M
Jung
Volker
V
Rahnenführer
Jörg
J
Schulz
Wolfgang A
WA
D000483:Alleles; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D019175:DNA Methylation; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D053319:Tumor Necrosis Factor Decoy Receptors / Q000235:genetics*
D058851:GPI-Linked Proteins; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C108661:TNFRSF10C protein, human; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D010749:Phosphoprotein Phosphatases