Genomic and expression analysis of the 3q25-q26 amplification unit reveals TLOC1/SEC62 as a probable target gene in prostate cancer.
Gain at chromosome 3q25-q26 has been reported to commonly occur in prostate cancer. To map the 3q25-q26 amplification unit and to identify the candidate genes of amplification, we did fluorescence in situ hybridization and quantitative real-time PCR for gene copy number and mRNA expression measurements in prostate cancer cell lines and prostate cancer samples from radical prostatectomy specimens. The minimal overlapping region of DNA copy number gains in the cell lines could be narrowed down to 700 kb at 3q26.2. Of all positional and functional candidates in this region, the gene TLOC1/SEC62 revealed the highest frequency (50%) of copy number gains in the prostate cancer samples and was found to be up-regulated at the mRNA level in all samples analyzed. TLOC1/Sec62 protein was also shown to be overexpressed by Western blot analysis. Intriguingly, the TLOC1/SEC62 gene copy number was increased in prostate tumors from patients who had a lower risk of and a longer time to progression following radical prostatectomy. These findings make TLOC1/SEC62 the best candidate within the 3q amplification unit in prostate cancer. TLOC1/Sec62 protein is a component of the endoplasmic reticulum protein translocation machinery, whose function during prostate carcinogenesis remains to be determined.
Jung
Volker
V
Clinic of Urology and Pediatric Urology, University of the Saarland, 66421 Homburg/Saar, Germany.
Kindich
Roland
R
Kamradt
Jörn
J
Jung
Martin
M
Müller
Mirko
M
Schulz
Wolfgang A
WA
Engers
Rainer
R
Unteregger
Gerhard
G
Stöckle
Michael
M
Zimmermann
Richard
R
Wullich
Bernd
B
D045744:Cell Line, Tumor; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005784:Gene Amplification; D018628:Gene Dosage; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation
D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C103676:SEC62 protein, human