Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer
The nucleolar protein dyskerin is involved in the modification of specific uridine residues to pseudouridine on ribosomal and small nuclear RNAs and in the stabilization of the telomerase RNA component (TERC). In this study we investigated for the first time the relationship between dyskerin express...
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Format: | Article |
Language: | English |
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Wiley
2008-01-01
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Series: | Cellular Oncology |
Online Access: | http://dx.doi.org/10.3233/CLO-2008-0436 |
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author | Lorenzo Montanaro Maria Calienni Claudio Ceccarelli Donatella Santini Mario Taffurelli Stefano Pileri Davide Treré Massimo Derenzini |
author_facet | Lorenzo Montanaro Maria Calienni Claudio Ceccarelli Donatella Santini Mario Taffurelli Stefano Pileri Davide Treré Massimo Derenzini |
author_sort | Lorenzo Montanaro |
collection | DOAJ |
description | The nucleolar protein dyskerin is involved in the modification of specific uridine residues to pseudouridine on ribosomal and small nuclear RNAs and in the stabilization of the telomerase RNA component (TERC). In this study we investigated for the first time the relationship between dyskerin expression and telomerase activity in a series of 61 primary breast carcinomas. We found that when dyskerin mRNA values were very low the telomerase activity was markedly reduced, independently of the expression of other important components of the telomerase complex such as telomerase reverse transcriptase (TERT). In vitro experiments showed that reduction of dyskerin expression affect telomerase activity through the reduction of TERC. Only when TERC levels were strongly reduced telomerase activity was hindered. Retroviral mediated over-expression of TERC abolished the telomerase impairment due to dyskerin knock down. In conclusion, our results indicated that, beside its effect on ribosome biogenesis, the levels of dyskerin in cancer cells modulate telomerase activity through the regulation of TERC levels, independently of TERT expression. This should be taken into consideration when utilizing TERT expression as a surrogate indicator of telomerase activity in tumour pathology. |
format | Article |
id | doaj-art-19f14a41f8a7427a8eeb3d78db538d27 |
institution | Kabale University |
issn | 1570-5870 1875-8606 |
language | English |
publishDate | 2008-01-01 |
publisher | Wiley |
record_format | Article |
series | Cellular Oncology |
spelling | doaj-art-19f14a41f8a7427a8eeb3d78db538d272025-02-03T01:11:11ZengWileyCellular Oncology1570-58701875-86062008-01-0130648349010.3233/CLO-2008-0436Relationship between Dyskerin Expression and Telomerase Activity in Human Breast CancerLorenzo Montanaro0Maria Calienni1Claudio Ceccarelli2Donatella Santini3Mario Taffurelli4Stefano Pileri5Davide Treré6Massimo Derenzini7Dipartimento di Patologia Sperimentale, Università di Bologna, Bologna, ItalyDipartimento di Patologia Sperimentale, Università di Bologna, Bologna, ItalyDipartimento Clinico di Scienze Radiologiche e Istocitopatologiche, Università di Bologna, Bologna, ItalyDipartimento Clinico di Scienze Radiologiche e Istocitopatologiche, Università di Bologna, Bologna, ItalyDipartimento di Scienze Chirurgiche e Anestesiologiche, Università di Bologna, Bologna, ItalyIstituto di Ematologia e Oncologia Medica “Lorenzo e Ariosto Seragnoli”, Università di Bologna, Bologna, ItalyDipartimento di Patologia Sperimentale, Università di Bologna, Bologna, ItalyDipartimento di Patologia Sperimentale, Università di Bologna, Bologna, ItalyThe nucleolar protein dyskerin is involved in the modification of specific uridine residues to pseudouridine on ribosomal and small nuclear RNAs and in the stabilization of the telomerase RNA component (TERC). In this study we investigated for the first time the relationship between dyskerin expression and telomerase activity in a series of 61 primary breast carcinomas. We found that when dyskerin mRNA values were very low the telomerase activity was markedly reduced, independently of the expression of other important components of the telomerase complex such as telomerase reverse transcriptase (TERT). In vitro experiments showed that reduction of dyskerin expression affect telomerase activity through the reduction of TERC. Only when TERC levels were strongly reduced telomerase activity was hindered. Retroviral mediated over-expression of TERC abolished the telomerase impairment due to dyskerin knock down. In conclusion, our results indicated that, beside its effect on ribosome biogenesis, the levels of dyskerin in cancer cells modulate telomerase activity through the regulation of TERC levels, independently of TERT expression. This should be taken into consideration when utilizing TERT expression as a surrogate indicator of telomerase activity in tumour pathology.http://dx.doi.org/10.3233/CLO-2008-0436 |
spellingShingle | Lorenzo Montanaro Maria Calienni Claudio Ceccarelli Donatella Santini Mario Taffurelli Stefano Pileri Davide Treré Massimo Derenzini Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer Cellular Oncology |
title | Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer |
title_full | Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer |
title_fullStr | Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer |
title_full_unstemmed | Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer |
title_short | Relationship between Dyskerin Expression and Telomerase Activity in Human Breast Cancer |
title_sort | relationship between dyskerin expression and telomerase activity in human breast cancer |
url | http://dx.doi.org/10.3233/CLO-2008-0436 |
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