Telomerase and hTERT: Can they serve as markers for gastric cancer diagnosis?
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AIM:To investigate telomerase activity and human telomerase reverse transcriptase (hTERT) expression in normal human gastric mucosal epithelial cells (nhG-MECs) and fibroblasts (nhGMFs).METHODS: nhGMECs and nhGMFs were isolated and cultured from specimens obtained during routine surgery for bleeding peptic ulcer.Telomerase activity in nhGMFs, nhGMECs, and the tumor cell lines BGC-823, SGC-7901 and MKN-28 cells was analyzed using the telomeric repeat amplification protocol assay.hTERT protein was determined in nhGMECs, nhGMFs, BGC-823, SGC-7901 and MKN-28 cells by indirect immunofluorescence. RESULTS:A similar level of telomerase activity was ob-served in nhGMECs, nhGMFs and BGC-823, SGC-7901, MKN-28 cell lines.Positive hTERT immunostaining was detected in nhGMECs, nhGMFs, BGC-823, SGC-7901 and MKN-28 cell lines. CONCLUSION:The use of telomerase or hTERT as diagnostic markers for gastric cancer may require further studies.Keywords:
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Activation of telomerase and stabilization of telomeres are considered to be necessary for immortalization of human tumor cells. Telomerase activity and telomere lengths were examined in adult and childhood cancer tissues. High telomerase activity was detected in over 40% samples. In these cases, the lengths of telomeres varied in wide range and the short telomere length significantly correlated with high proliferative index. The patients with short telomeres demonstrated poorer prognosis than other patients. These findings suggest that the short telomeres might be related with the malignant potential in cancers with high telomerase activity.
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Abstract. The ribonucleoprotein, telomerase, is responsible for the maintenance of telomere length in most immortal and cancer cells. Telomerase appears to be a marker of human malignancy with at least 85% of human cancers expressing its activity. In the present study, we examined a series of tumor‐derived and in vitro immortalized cell lines for telomerase activity levels, telomere lengths, and expression levels of the RNA and catalytic components of telomerase. We found significant variability in both telomere lengths and telomerase activity in clones from tumor cells. In addition, the levels of telomerase components or telomerase activity were not predictive of telomere length. Data from clonally derived cells suggest that critically shortened telomeres in these tumor‐derived cell lines may signal activation of telomerase activity through an increase in the expression of the catalytic subunit of telomerase. Although clones with low telomerase shorten their telomeres over time, their subclones all have high levels of telomerase activity with no telomere shortening. In addition, analysis of early clones for telomerase activity indicates substantial variability, which suggests that activity levels fluctuate in individual cells. Our data imply that cell populations exhibit a cyclic expression of telomerase activity, which may be partially regulated by telomere shortening.
Telomerase RNA component
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HeLa
Senescence
Telomere-binding protein
Telomerase RNA component
Immortalised cell line
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Immortalised cell line
Telomerase RNA component
Telomere-binding protein
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There is increasing evidence that telomere shortening both in vitro and in vivo is the clock that counts cell divisions and determines the onset of cellular senescence. Cells overcome the normal senescence mechanism by stabilising telomere length; probably due to the activity of telomerase activity that specifically elongates telomeres. Most human primary tumors contain telomerase, while the cells of most normal tissues lack this activity. Normal haematopoietic cells express telomerase activity. This review is a discussion of utility of telomere length and telomerase activity measurements in the diagnostics and prognosis of leukaemia as well as the potential value of antitelomerase therapy. Results of telomere lengths measurements in young recipients of allogenic transplants are also reported.
Senescence
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Telomere length maintenance is essential for cellular immortalization, and thus tumorigenesis. Most human tumors and immortal cell lines maintain their telomeric DNA via the activity of a specialized reverse transcriptase, telomerase. Stabilization of telomeric repeat tracts may also be achieved through a telomerase-independent mechanism, referred to as alternative lengthening of telomeres (ALT). ALT cells are telomerase negative and are characterized by extremely long and heterogeneously sized telomeres and novel multiprotein structures called ALT-associated PML nuclear bodies which are unique to ALT cells. To determine if reconstitution of telomerase activity suppressed ALT and restored wild-type telomere lengths, we introduced the catalytic subunit of telomerase into two ALT cell lines. Initially, two clonal lines exhibited enrichment of shorter telomeres while maintaining a population of ultra-long telomeres similar to that observed in the parental line, suggesting that telomerase is stabilizing the shorter telomeres in the population. Telomere length in the third clonal line was not detectably different from that in the parental cell line. One clonal line with a phenotype of shorter telomeres maintained this pattern over time in culture while the second gradually reverted to the parental ALT telomere length pattern, concurrent with reduction of telomerase activity. All clones continued to maintain ALT-associated PML nuclear bodies regardless of whether telomerase was present. The data suggest that introduction of telomerase activity alone is not sufficient to completely repress ALT, that telomerase acts preferentially on the shortest telomeres in the culture and that the ALT and telomerase pathways may be present concurrently in mammalian cells.
Telomerase RNA component
Telomere-binding protein
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Telomere-binding protein
Telomerase RNA component
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Telomerase RNA component
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The ribonucleoprotein, telomerase, is responsible for the maintenance of telomere length in most immortal and cancer cells. Telomerase appears to be a marker of human malignancy with at least 85% of human cancers expressing its activity. In the present study, we examined a series of tumor-derived and in vitro immortalized cell lines for telomerase activity levels, telomere lengths, and expression levels of the RNA and catalytic components of telomerase. We found significant variability in both telomere lengths and telomerase activity in clones from tumor cells. In addition, the levels of telomerase components or telomerase activity were not predictive of telomere length. Data from clonally derived cells suggest that critically shortened telomeres in these tumor-derived cell lines may signal activation of telomerase activity through an increase in the expression of the catalytic subunit of telomerase. Although clones with low telomerase shorten their telomeres over time, their subclones all have high levels of telomerase activity with no telomere shortening. In addition, analysis of early clones for telomerase activity indicates substantial variability, which suggests that activity levels fluctuate in individual cells. Our data imply that cell populations exhibit a cyclic expression of telomerase activity, which may be partially regulated by telomere shortening.
Telomerase RNA component
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