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

J Pathol. 2006 Sep;210(1):10-8. doi: 10.1002/path.2023.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Silencing
  • Humans
  • Immunohistochemistry / methods
  • Lung Neoplasms / genetics
  • Lymphoma, B-Cell / genetics
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins / genetics*
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis*
  • RNA, Ribosomal / analysis*
  • Telomerase / genetics*


  • Cell Cycle Proteins
  • DKC1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • RNA, Ribosomal
  • Telomerase