Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer

Lorenzo Montanaro, M. Brigotti, J. Clohessy, S. Barbieri, C. Ceccarelli, D. Santini, M. Taffurelli, M. Calienni, J. Teruya-Feldstien, D. Trerè, P. P. Pandolfi, M. Derenzini

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Dyskerin is a nucleolar protein, altered in dyskeratosis congenita, which carries out two separate functions, both fundamental for proliferating cells. One function is the pseudo-uridylation of ribosomal RNA (rRNA) molecules, necessary for their processing, and the other is the stabilization of the telomerase RNA component, necessary for telomerase activity. A significant feature of dyskeratosis congenita is an increased susceptibility to cancer; so far, however, no data have been reported on dyskerin changes in human tumours. Therefore, in this study, the distribution of dyskerin in a large series of human tumours from the lung, breast, and colon, as well as from B-cell lymphomas, was analysed by immunohistochemistry. Dyskerin proved never to be lost or delocalized outside the nucleolus. A quantitative analysis of dyskerin mRNA expression was then performed in 70 breast carcinomas together with the evaluation of telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin mRNA levels were highly variable and directly associated with both telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin gene silencing in the MCF-7 human breast carcinoma cell line reduced telomerase activity and rRNA pseudo-uridylation. Significantly, patients with low dyskerin expression were characterized by a better clinical outcome than those with a high dyskerin level. These data indicate that dyskerin is not lost in human cancers and that the levels of its expression and function are associated with tumour progression.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalJournal of Pathology
Volume210
Issue number1
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Cancer
  • Dyskerin
  • Telomerase
  • rRNA processing

Fingerprint

Dive into the research topics of 'Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer'. Together they form a unique fingerprint.

Cite this