Telomerase activity and telomere length in different areas of renal cell carcinoma

Fiedler, Wolfgang; Dahse, Regine; Schlichter, A.; Junker, Kerstin; Kosmehl, Hartwig; Ernst, Germana; Schubert, Jöerg; Claussen, Uwe

doi:10.3892/ijo.9.6.1227

Cited by 11 publications

(12 citation statements)

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“…Telomerase activity and expression of its catalytic counterpart (hTERT) appear now to be associated with cell transformation and to display significant prognostic value in several human cancers, including breast and gastric carcinomas and neuroblastomas2, 11, 12, 28, 29. Up to now, studies investigating tumour progression and clinical outcome in renal cancers had detected telomerase activity in RCC, but failed to reveal an obvious association between the presence of telomerase activity and clinicopathological parameters13–17. To gain further insights into the potential value of telomerase in the prognosis of renal malignancies, we aimed, in a series of 41 RCC, to analyse quantitatively mRNA expression of hTERT, which is considered as the rate limiting factor for telomerase activity.…”

Section: Discussionmentioning

confidence: 99%

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hTERT expression in sporadic renal cell carcinomas

Paradis¹,

Bièche²,

Dargère³

et al. 2001

J. Pathol.

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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.

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Section: Discussionmentioning

confidence: 99%

“…Thus, telomerase activity has been detected in various cancers and has been found in some to be prognostically relevant11, 12. In RCC, several studies reported telomerase activity in as many as 70% of cases, but failed to show any correlations with usual prognostic histopathological factors13–17.…”

Section: Introductionmentioning

confidence: 99%

hTERT expression in sporadic renal cell carcinomas

Paradis¹,

Bièche²,

Dargère³

et al. 2001

J. Pathol.

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“…In this way we analyzed eight cases that had been well characterized by other molecular and histopathological investigations [13,14]. In tumor tissue, several proteins were identified that appeared to be either characteristic for the tumor (peaks were present in both peripheral and central tumor tissues but not in normal tissue) or normal tissue.…”

Section: Resultsmentioning

confidence: 99%

“…In several studies on genetic alterations of RCC it has been shown, that specific types of RCC and also different steps of tumor development and progression are characterized by specific genetic alterations [13,14]. But until now, there are no prognostic parameters allowing for an individual risk assessment concerning the clinical course of disease or to estimate the individual therapy response in patients with RCC.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometry meets chip technology: A new proteomic tool in cancer research?

Eggeling¹,

et al. 2001

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DNA chip technologies are the most exiting genomic tools, which were developed within the last few years. It is, however, evident that knowledge of the gene sequence or the quantity of gene expression is not sufficient to predict the biological nature and function of a protein. This can be particularly important in cancer research where post-translational modifications of a protein can specifically contribute to the disease. To address this problem, several proteomic tools have been developed. Currently the most widely used proteomic tool is two-dimensional protein gel electrophoresis (2-DE), which can display protein expression patterns to a high degree of resolution. As an alternative to 2-DE, a preliminary study using a new technique was employed to generate protein expression patterns from whole tissue extracts. Surface-enhanced laser desorption/ionization (SELDI) allows the retention of proteins on a solid-phase chromatographic surface (ProteinChip Array) with direct detection of retained proteins by time of flight-mass spectrometry (TOF-MS). Using this system, we analyzed eight cases of renal cell carcinoma (RCC) including normal, peripheral and central tumor tissue as well as four microdissected cases of cervical intraepithelial neoplasia (CIN) and three microdissected cases of cervix uteri carcinoma. Differentially expressed proteins were found by comparing the protein expression patterns generated using SELDI-based TOF-MS of tumor tissue with normal and neoplastic tissue, respectively. By applying this fast and powerful ProteinChip array technology it becomes possible to investigate complex changes at the protein level in cancer associated with tumor development and progression.

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“…However, two other studies did not find telomerase activity in samples of benign prostatic hyperplasia (134,135). Other tissues where telomerase activation may be an early event in neoplasia are colorectal (136,137), bladder (125) and kidney tissue (138,139).…”

Section: Telomerase As a Tumour Markermentioning

confidence: 94%

Telomerase in cancer: Clinical applications

Urquidi¹,

Tarin²,

Goodison³

1998

Annals of Medicine

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The biology of telomeres and telomerase has been the subject of intensive investigative effort since it became evident that they play a significant role in two important biological processes, the loss of cellular replicative capacity inherent to organismal ageing and the unrestricted cell proliferation characteristic of carcinogenesis. Telomere shortening in normal cells is a result of DNA replication events, and reduction beyond a critical length is a signal for cellular senescence. One of the cellular mechanisms used to overcome proliferative restriction is the activation of the enzyme telomerase, which replaces the loss of telomeric DNA that occurs at each cell division. Studies have demonstrated that tumours have shorter telomeres than normal tissue and that telomerase is activated in up to 90% of all human cancers while it is present only in a limited range of normal adult tissues. The role of telomerase in the extension of the cellular replicative lifespan has recently been shown by ectopic expression of the enzyme, being consistent with the oncogenesis model whereby the acquisition of an 'immortal' phenotype is a requirement for advanced tumour progression. In this article we review the present knowledge of telomeres and telomerase in cancer and discuss the potential use of this enzyme as a diagnostic and prognostic tumour marker and as a target for cancer therapy.

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Telomerase activity and telomere length in different areas of renal cell carcinoma

Cited by 11 publications

References 0 publications

hTERT expression in sporadic renal cell carcinomas

hTERT expression in sporadic renal cell carcinomas

Mass spectrometry meets chip technology: A new proteomic tool in cancer research?

Telomerase in cancer: Clinical applications

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