Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer Journal Article
| Authors: | Montanaro, L.; Brigotti, M.; Clohessy, J.; Barbieri, S.; Ceccarelli, C.; Santini, D.; Taffurelli, M.; Calienni, M.; Teruya-Feldstein, J.; Trerè, D.; Pandolfi, P. P.; Derenzini, M. |
| Article Title: | Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer |
| 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. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| Keywords: | immunohistochemistry; controlled study; human tissue; protein expression; human cell; major clinical study; histopathology; outcome assessment; protein function; protein localization; protein analysis; protein blood level; cell cycle proteins; breast cancer; carcinoma, non-small-cell lung; lung neoplasms; neoplasm proteins; colonic neoplasms; cancer cell culture; enzyme activity; cell line, tumor; breast neoplasms; telomerase; nuclear proteins; rna; gene expression regulation, neoplastic; lymphoma, b-cell; statistical significance; messenger rna; rna, messenger; quantitative analysis; gene silencing; ribosome rna; rna, ribosomal; cell strain mcf 7; breast carcinogenesis; rna, neoplasm; nucleolus; rrna processing; dyskerin |
| Journal Title: | Journal of Pathology |
| Volume: | 210 |
| Issue: | 1 |
| ISSN: | 0022-3417 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2006-09-01 |
| Start Page: | 10 |
| End Page: | 18 |
| Language: | English |
| DOI: | 10.1002/path.2023 |
| PUBMED: | 16841302 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 4 June 2012" - "CODEN: JPTLA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work