Relationship between dyskerin expression and telomerase activity in human breast cancer

Lorenzo Montanaro, Maria Calienni, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Stefano Pileri, Davide Treré, Massimo Derenzini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)483-490
Number of pages8
JournalCellular Oncology
Volume30
Issue number6
DOIs
Publication statusPublished - 2008

Keywords

  • Breast carcinomas
  • Dyskerin
  • Telomerase
  • TERC
  • TERT

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine

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