Telomerase activity and hTERT mRNA in development and progression of adenoma to colorectal cancer

Kanamaru, Taichi; Tanaka, Kenichi; Kotani, Joji; Ueno, Koji; Yamamoto, Masahiro; Idei, Yuka; Higuchi, Hisashi; Takeyama, Yoshifumi

doi:10.3892/ijmm.10.2.205

Cited by 23 publications

(23 citation statements)

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“…A similar scenario ( Fig. 2 c) is seen when comparing the mean frequencies of anaphase bridging to telomerase activity in colorectal neoplasms (Yoshida et al, 1999;Kanamaru et al, 2002). Here, the rate of anaphase bridging is elevated compared to normal tissue already in low-grade dysplastic polyps, is further elevated in high-grade pre-invasive lesions and invasive carcinomas, and finally decreases in carcinoma metastases (Rudolph et al, 2001).…”

Section: Is Telomerase Activation Too Late?mentioning

confidence: 56%

“…( b ) The respective proportions of urothelial cancers showing anaphase bridges (red circles) and telomerase activity by TRAP assay (blue circles) at preinvasive (Ta-T1) and invasive (T2-T4) stages (De Kok et al, 2000;Longchampt et al, 2003;Gisselsson et al, unpublished data). ( c ) Mean frequencies of anaphase bridges (AB; red circles) and mean telomerase activity (TA) by TRAP assay (blue circles) during colorectal carcinogenesis; N = normal epithelium, LGA = low grade dysplastic adenoma, HGA = high-grade dysplastic adenoma, CIS = carcinoma in situ; ICA = invasive carcinoma; MET = metastasis (Yoshida et al, 1999;Rudolph et al, 2001;Kanamaru et al, 2002). ously increases during neoplastic progression, reaching maximum values in metastatic tumours. Taken together these studies indicate that telomere shortening occurs early in tumorigenesis, and reaches high levels before telomerase activation through up-regulation of TERT reaches maximum levels.…”

Section: Is Telomerase Activation Too Late?mentioning

confidence: 99%

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Telomere dysfunction and telomerase activation in cancer – a pathological paradox?

Calcagnile¹,

Gisselsson²

2007

Cytogenet Genome Res

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Telomerase is expressed in more than 90% of human cancers. Telomere maintenance by this enzyme is believed to safeguard genomic integrity in neoplastic cells. Nevertheless, many telomerase-expressing tumours exhibit chromosomal instability triggered by short, dysfunctional telomeres, implying that active telomerase is not sufficient for preserving a functional telosomic nucleoprotein complex in cancer cells. We here examine three possible solutions to this ostensible paradox. First, prior to telomerase activation, telomere erosion may have evolved to a level where telomeric repeat sequences are too short to provide a functional substrate for telomerase enzyme activity. Second, mechanisms other than the continuous telomere erosion counteracted by telomerase may contribute to rapid shortening of telomere repeats. Third, dysfunction of telomere-regulating proteins may result in direct telomere uncapping. Moreover, telomerase may contribute to tumour development also through mechanisms unrelated to telomere length maintenance. Taken together, the available data on the role of telomerase in cancer strongly support that inhibition of this enzyme is a feasible strategy for cancer therapy.

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Section: Is Telomerase Activation Too Late?mentioning

confidence: 56%

Section: Is Telomerase Activation Too Late?mentioning

confidence: 99%

Telomere dysfunction and telomerase activation in cancer – a pathological paradox?

Calcagnile¹,

Gisselsson²

2007

Cytogenet Genome Res

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“…The majority of studies found upregulation of telomerase activity and mRNA expression in colorectal tumors, 17,[35][36][37] while others found increased activity only in late events during carcinogenesis but not in preneoplastic lesions. 38,39 In this context, contradictory results have been found in patients with UC. [40][41][42] In our study, the level of hTERT mRNA was significantly increased in CRC samples and in human tumor xenografts but not in the samples of UC patients with and without neoplasia.…”

Section: Discussionmentioning

confidence: 85%

Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia

Švec

Musı́lková

Bryndová

et al. 2010

Inflammatory Bowel Diseases

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“…Discrepancies between both parameters, such as in one of our patients with low telomerase activity (not due to telomerase/PCR inhibitors as tested always by serial dilutions) but high expression of hTERT, might indicate the presence of spliced hTERT variants (36), abnormalities in the RNA template, or post-transcriptional modifications of the different telomerase subunits (35), which have been reported recently. Such occasional discordance between telomerase activity and hTERT mRNA has been also observed in several other types of tumors (37). Therefore, it appears prudent to use direct activity measurements to determine unequivocally the presence of telomerase.…”

Section: Discussionmentioning

confidence: 99%

Telomerase Activity in Cell Lines of Pediatric Soft Tissue Sarcomas

et al. 2003

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Telomeres and their maintenance by telomerase have been implicated to play an important role in carcinogenesis. As almost all malignant tumors express telomerase (in contrast to normal somatic cells), assessment of its activity has been proposed as a diagnostic and prognostic tool. To test the prognostic value of telomerase in pediatric soft tissue sarcoma (STS), we analyzed telomere length (by telomere restriction fragment analysis), telomerase activity (by modified telomerase repeat amplification protocol assay), and expression of human telomerase reverse transcriptase (hTERT) mRNA (by TaqMan technique) in cell lines of different types of STS from 12 children and adolescents. Telomere length (3.7-9.0 kb) showed a very heterogeneous pattern, independent of subtype of STS or the age of the patients, and it was not associated with expression of hTERT mRNA. In contrast, there was a trend of an association between hTERT and telomerase activity. The three tested cell lines of embryonal rhabdomyosarcomas demonstrated no or low (n ϭ 2) telomerase activity, which was confirmed in two cases by a very low expression of hTERT mRNA. Thus, we suggest that the significant difference (p Ͻ 0.01) in the less aggressive clinical behavior of embryonal rhabdomyosarcomas in comparison to other subtypes may be due to differences in telomerase expression. Taken together, our cell line experiments imply that telomerase activity might be a biologic marker for stratification between STS with different clinical prognosis. Abbreviations TRF, telomere restriction fragment TRAP, telomerase repeat amplification protocol STS, soft tissue sarcoma hTERT, human telomerase reverse transcriptase RME, embryonal rhabdomyosarcoma RMA, alveolar rhabdomyosarcoma PNET, peripheral neuroectodermal tumor RT, rhabdoid tumorThere is now increasing evidence that maintenance of telomeres plays an important role during cellular aging and carcinogenesis (1, 2). Telomeres represent the end of chromosomes and consist of repetitive nucleotide units with the sequence (TTAGGG) n . They serve to protect linear chromosomes from damage and provide the structural basis for solving the socalled "end replication problem" (3, 4). With each cell division, telomeres show a progressive loss of their length, and at a critical limit normally cells stop dividing and enter senescence (1, 4). Such critical shortening can be prevented by the multisubunit enzyme telomerase comprised of a RNA template component (hTR), the catalytic reverse transcriptase component (hTERT), and regulatory proteins (5). The ribonucleoprotein telomerase adds additional TTAGGG repeats at the ends of telomeres and its activity is down-regulated in most postembryonic cell types (6). However, in most cancer cells telomerase expression is activated, and this can lead to cellular immortalization. Thus, acquisition of telomerase activity is a crucial step in restoring the replicative potential of cells and in initiating human cell transformation (7).Therefore, telomerase has been a focus in cancer research, espe...

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Telomerase activity and hTERT mRNA in development and progression of adenoma to colorectal cancer

Cited by 23 publications

References 0 publications

Telomere dysfunction and telomerase activation in cancer – a pathological paradox?

Telomere dysfunction and telomerase activation in cancer – a pathological paradox?

Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia

Telomerase Activity in Cell Lines of Pediatric Soft Tissue Sarcomas

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