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...

Full description

Saved in:
Bibliographic Details
Main Authors: Lorenzo Montanaro, Maria Calienni, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Stefano Pileri, Davide Treré, Massimo Derenzini
Format: Article
Language:English
Published: Wiley 2008-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.3233/CLO-2008-0436
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832564387786784768
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
work_keys_str_mv AT lorenzomontanaro relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT mariacalienni relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT claudioceccarelli relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT donatellasantini relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT mariotaffurelli relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT stefanopileri relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT davidetrere relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer
AT massimoderenzini relationshipbetweendyskerinexpressionandtelomeraseactivityinhumanbreastcancer