hTERT expression in sporadic renal cell carcinomas.
Human telomerase is a specialized reverse transcriptase that catalyses telomeric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and one of its components, hTERT, is considered as the rate-limiting factor. While telomerase activity was found to be prognostically relevant in various cancers, results obtained from renal cell carcinomas (RCC) failed to show any correlation with the usual prognostic factors. The aim of the study was to reassess the role of telomerase and its hTERT component in the biological behaviour of RCC using new quantitative techniques, such as the quantitative evaluation of hTERT mRNA level by a real-time RT-PCR procedure and the measuring of telomerase activity by an ELISA TRAP assay. Since experimental evidence supports a relationship between cell proliferation or c-myc expression and telomerase, the proliferation index and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were studied. In 73% of cases, normalized hTERT mRNA expression was significantly higher in the tumour sample than in the normal tissue. Telomerase activity was detected in 63% of RCC, while corresponding normal tissue was always negative. Analysis of correlations showed firstly that both telomerase activity and hTERT mRNA level were lower in the group of CRCC versus non-CRCC (TRAP: 0.3+/-0.1 versus 0.6+/-0.2, p<0.05; hTERT/PO mRNA: 5+/-3 versus 37+/-8, p<0.001, respectively); secondly, that in the group of CRCC, hTERT mRNA expression level was correlated with the stage of the tumour (p=0.01); and thirdly, that no correlation was observed between c-myc mRNA level and hTERT mRNA level. In conclusion, these results support the involvement of telomerase in RCC and the potential interest of hTERT mRNA quantification.
Paradis
V
V
Service d'Anatomie Pathologique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, UPRES EA 1602, Faculté de Médecine, Paris-sud, France. vparadis@teaser.fr
Bièche
I
I
Dargère
D
D
Bonvoust
F
F
Ferlicot
S
S
Olivi
M
M
Lagha
N B
NB
Blanchet
P
P
Benoît
G
G
Vidaud
M
M
Bedossa
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase