Telomerase activity and telomerase subunit gene expression levels are not related in prostate cancer: a real-time quantification and in situ hybridization study.
Because the mechanisms of telomerase activation in prostate cancer are mainly unknown, we investigated the relationships between telomerase activity and expression levels of human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) mRNA in benign and malignant alterations of the human prostate gland. Using the LightCycler technology, hTERT mRNA expression was quantified in 46 radical prostatectomy and 10 benign prostatic hyperplasia (BPH) cases; hTR expression was quantified in a subset of these tissue samples. Telomerase activity was measured using a quantitative telomeric repeat amplification protocol ELISA assay. Similar to hTR, which was expressed in all tissue samples tested, hTERT mRNA was detected in 98% of the prostate cancer samples and in 30% of the BPH samples. Regarding clinicopathologic variables, telomerase activity was significantly correlated with Gleason score (<7 vs > or =7, p = 0.02). No relationships emerged between normalized hTR or hTERT expression levels and tumor stage, Gleason score, lymph node status, or preoperative serum prostate-specific antigen. Remarkably, one third of all cancer and BPH tissue samples with hTR and hTERT expression lack telomerase activity. Quantitative analyses contradict the assumption that a certain threshold level of hTR or hTERT mRNA is required for telomerase activation, thus indicating that telomerase regulation in prostate cancer occurs more likely on a posttranscriptional level. Nevertheless, the observation that hTR and hTERT mRNA levels are significantly (p < 0.002) correlated suggests some common mechanisms in the up-regulation of hTR and hTERT expression. Because in situ hybridization revealed strong hTERT expression in all cells of the tumor glands but also in high-grade prostatic intraepithelial neoplasia foci, this up-regulation seems to occur early in prostate carcinogenesis.
Clinic of Urology and Pediatric Urology, University of the Saarland, Homburg/Saar, Germany.
Joern
J
Kamradt
Carsten
C
Drosse
Sascha
S
Kalkbrenner
Volker
V
Rohde
Ramona
R
Lensch
Jan
J
Lehmann
Thomas
T
Fixemer
Helmut
H
Bonkhoff
Michael
M
Stoeckle
Bernd
B
Wullich
D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D021122:Protein Subunits; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase