hTERT expression in sporadic renal cell carcinomas

Abstract

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.

Differential Expression of Full-length Telomerase Reverse Transcriptase mRNA and Telomerase Activity between Normal and Malignant Renal Tissues

“…Earlier clinical investigations have shown that telomerase activity is only detectable in RCC tumors but not in adjacent normal renal tissues, however, both normal and malignant tissues may express hTERT mRNA, a rate-limiting component for telomerase activity (11,15,17). To determine whether this was also the case for our cohort of patients, we employed the specific hTERT primers 1,784/1,928, used in above studies (15,17), to PCR amplify hTERT transcripts in 33 RCC tumors and their corresponding normal tissues.…”

The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma

“…Concordantly, a significant association between full length hTERT RNA, telomerase activity and cMyc induction in RCC was recently demonstrated, further strengthening the connection between cMyc and hTERT. 23 In contrast, a smaller series of RCC showed no correlation between cMyc and hTERT mRNA levels 22 but indicated that cRCC had lower hTERT and telomerase activity levels than nonccRCC. The latter finding is obviously in contrast to our analysis, which was based on a larger series of tumors.…”

“…21 However, inconsistent observations have been noted regarding a connection between cMyc and hTERT gene expression in RCC. 22,23 PKB/Akt can also affect telomerase expression through post-transcriptional phosphorylation of the hTERT protein as indicated in studies on myeloma and ovarian cancer cells. 24,25 Thus, the PI-3-kinase-PKB/Akt pathway can interact with hTERT and telomerase expression at both the transcriptional and posttranscriptional level and since DJ-1 might be a potentially important regulator of this pathway the present study was undertaken to further investigate this issue in RCC.…”

Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours

“…A requirement of 70 -80% of cancer cells seems reasonable in order to compare telomerase levels to external standards provided by cell lines (Marchetti et al, 2002). Furthermore, the exactitude of any measurement of telomerase activity is challenged by intratumoral heterogeneity of hTERT expression (Kumaki et al, 2001;Paradis et al, 2001). We and others have experienced successful hTERT in situ hybridisation approaches, which evaluate the level of transcription of hTERT (Kolquist et al, 1998;Soria et al, 2001;Wang et al, 2002).…”