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Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma
Association with cyclooxygenase-2 and prognosis
Article first published online: 2 OCT 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 10, pages 2761–2769, 15 November 2008
How to Cite
Stoppoloni, D., Cardillo, I., Verdina, A., Vincenzi, B., Menegozzo, S., Santini, M., Sacchi, A., Baldi, A. and Galati, R. (2008), Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma. Cancer, 113: 2761–2769. doi: 10.1002/cncr.23904
- Issue published online: 3 NOV 2008
- Article first published online: 2 OCT 2008
- Manuscript Accepted: 3 JUL 2008
- Manuscript Revised: 19 JUN 2008
- Manuscript Received: 29 APR 2008
- Associazione Italiana per la Ricerca sol Cancro
- Ministry of Health
- Ministry of University
- human embryonic lethal abnormal vision-like protein;
The human embryonic lethal abnormal vision (ELAV)-like protein HuR is a messenger RNA (mRNA)-binding protein that controls the stability of certain transcripts, including cyclooxygenase2 (COX-2).
To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to COX-2 over expression in mesothelioma, the authors studied expression of COX-2 and HuR in 5 mesothelioma cell lines (MSTO, NCI, Ist-Mes1, Ist-Mes2, and MPP89) and in a group of 29 human mesothelioma specimens that were characterized previously for COX-2 expression.
All 5 cell lines expressed HuR, whereas COX-2 was not detectable in MSTO or NCI cells. Treatment with cytokines induced a shift in systolic HuR protein levels in MPP89 and Ist-Mes2 cells that was accompanied by an increase in the expression of COX-2 mRNA and protein. In Ist-Mes1 cells, cytokine stimulation did not cause the passage of HuR from nucleus to cytoplasm, and the synthesis of COX-2 did not increase. In tumor tissues, immunohistochemistry revealed a positive, statistically significant correlation between high COX-2 expression and cytoplasmic localization of HuR (P = .016). Moreover, on univariate analysis, overall survival was found to be influenced strongly by cytoplasmic HuR localization (P = .004).
The current results suggested that HuR plays a role in tumor progression in mesothelioma and that COX-2 may be a target of its activity in neoplastic cells. Together, these observations indicate that strategies aiming toward the modulation of HuR may have a potential clinical benefit in mesothelioma. Cancer 2008. © 2008 American Cancer Society.