RAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancer.
To detect genes that are overexpressed in prostate cancer, a subtracted cDNA library was first constructed from the PC-3 cell line and subsequently screened by using cDNA microarray hybridization. Sixty-eight genes were found to be overexpressed (ratio>3) in PC-3. Half of these genes were in chromosomal regions, which, using comparative genomic hybridization, we previously showed to be gained in PC-3. Subsequently, the expression and copy number of selected genes were studied by quantitative RT-PCR and fluorescence in situ hybridization in prostate cancer cell lines, xenografts, and clinical tumor specimens of benign prostate hyperplasia and untreated as well as hormone-refractory prostate carcinomas. Two genes from chromosomal region 8q24-RAD21 and KIAA0196-showed increased expression in clinical prostate carcinomas and were also amplified in 30-40% of xenografts and hormone-refractory tumors. In addition, the expression of KIAA0196 was significantly (P=0.0051) higher in tumors with the gene amplification than in those without it. The data suggest that KIAA0196 and possibly RAD21 are putative target genes for the common amplification of 8q23-24 in prostate cancer.
Porkka
Kati P
KP
Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Tammela
Teuvo L J
TL
Vessella
Robert L
RL
Visakorpi
Tapio
T
D015152:Blotting, Northern; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D005784:Gene Amplification; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human