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Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells

Telomerase, an enzyme that adds hexameric repeats of 5′‐TTAGGG‐3′, termed telomeres, to the ends of chromosomal DNA, has been implicated in cellular immortalization and cellular senescence. Recently several relevant genes have been cloned, including those encoding three major components of human tel...

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Autores principales: Yamada, Koji, Yajima, Tomomi, Yagihashi, Atsuhito, Kobayashi, Daisuke, Koyanagi, Yoko, Asanuma, Koichi, Yamada, Mikako, Moriai, Ryosuke, Kameshima, Hidekazu, Watanabe, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926307/
https://www.ncbi.nlm.nih.gov/pubmed/11123427
http://dx.doi.org/10.1111/j.1349-7006.2000.tb00915.x
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author Yamada, Koji
Yajima, Tomomi
Yagihashi, Atsuhito
Kobayashi, Daisuke
Koyanagi, Yoko
Asanuma, Koichi
Yamada, Mikako
Moriai, Ryosuke
Kameshima, Hidekazu
Watanabe, Naoki
author_facet Yamada, Koji
Yajima, Tomomi
Yagihashi, Atsuhito
Kobayashi, Daisuke
Koyanagi, Yoko
Asanuma, Koichi
Yamada, Mikako
Moriai, Ryosuke
Kameshima, Hidekazu
Watanabe, Naoki
author_sort Yamada, Koji
collection PubMed
description Telomerase, an enzyme that adds hexameric repeats of 5′‐TTAGGG‐3′, termed telomeres, to the ends of chromosomal DNA, has been implicated in cellular immortalization and cellular senescence. Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase‐associated protein‐1 (TEP1). Also important are genes encoding human telomeric‐repeat binding factor proteins (TRF) 1 and 2. We compared 10 human malignant hematopoietic cell lines, 19 samples from patients with acute leukemia and normal granulocytes and monocytes to study telomerase activity and expression of these various genes using a reverse transcription‐polymerase chain reaction (RT‐PCR). In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected. TEP1 mRNA was expressed in normal monocytes, but not granulocytes. Expression of TRF1 and TRF2 mRNAs was greater in the normal cells than in human malignant hematopoietic cell lines and in 16 samples of patients with acute leukemia. When differentiation of the malignant hematopoietic cell line HL‐60 was induced using tumor‐necrosis‐factor 471 and all‐trans retinoic acid (ATRA), telomerase activity decreased gradually during differentiation. Of the three telomerase components, only hTERT mRNA expression showed changes paralleling telomerase activity, becoming undetectable with differentiation. In contrast, initially low expression of TRF1 and TRF2 mRNAs increased during differentiation. Not only hTERT, but also TRF1 and TRF2 are important regulators of telomerase activity that represent potential targets for gene therapy against cancer.
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spelling pubmed-59263072018-05-11 Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells Yamada, Koji Yajima, Tomomi Yagihashi, Atsuhito Kobayashi, Daisuke Koyanagi, Yoko Asanuma, Koichi Yamada, Mikako Moriai, Ryosuke Kameshima, Hidekazu Watanabe, Naoki Jpn J Cancer Res Article Telomerase, an enzyme that adds hexameric repeats of 5′‐TTAGGG‐3′, termed telomeres, to the ends of chromosomal DNA, has been implicated in cellular immortalization and cellular senescence. Recently several relevant genes have been cloned, including those encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase‐associated protein‐1 (TEP1). Also important are genes encoding human telomeric‐repeat binding factor proteins (TRF) 1 and 2. We compared 10 human malignant hematopoietic cell lines, 19 samples from patients with acute leukemia and normal granulocytes and monocytes to study telomerase activity and expression of these various genes using a reverse transcription‐polymerase chain reaction (RT‐PCR). In all 10 malignant cell lines with telomerase activity, hTR, hTERT mRNA, and TEP1 mRNA were expressed, while in normal monocytes and granulocytes without telomerase activity, expression of hTR, but not hTERT mRNA was detected. TEP1 mRNA was expressed in normal monocytes, but not granulocytes. Expression of TRF1 and TRF2 mRNAs was greater in the normal cells than in human malignant hematopoietic cell lines and in 16 samples of patients with acute leukemia. When differentiation of the malignant hematopoietic cell line HL‐60 was induced using tumor‐necrosis‐factor 471 and all‐trans retinoic acid (ATRA), telomerase activity decreased gradually during differentiation. Of the three telomerase components, only hTERT mRNA expression showed changes paralleling telomerase activity, becoming undetectable with differentiation. In contrast, initially low expression of TRF1 and TRF2 mRNAs increased during differentiation. Not only hTERT, but also TRF1 and TRF2 are important regulators of telomerase activity that represent potential targets for gene therapy against cancer. Blackwell Publishing Ltd 2000-12 /pmc/articles/PMC5926307/ /pubmed/11123427 http://dx.doi.org/10.1111/j.1349-7006.2000.tb00915.x Text en
spellingShingle Article
Yamada, Koji
Yajima, Tomomi
Yagihashi, Atsuhito
Kobayashi, Daisuke
Koyanagi, Yoko
Asanuma, Koichi
Yamada, Mikako
Moriai, Ryosuke
Kameshima, Hidekazu
Watanabe, Naoki
Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title_full Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title_fullStr Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title_full_unstemmed Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title_short Role of Human Telomerase Reverse Transcriptase and Telomeric‐repeat Binding Factor Proteins 1 and 2 in Human Hematopoietic Cells
title_sort role of human telomerase reverse transcriptase and telomeric‐repeat binding factor proteins 1 and 2 in human hematopoietic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926307/
https://www.ncbi.nlm.nih.gov/pubmed/11123427
http://dx.doi.org/10.1111/j.1349-7006.2000.tb00915.x
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