Journal
CANCER
Volume 113, Issue 10, Pages 2761-2769Publisher
WILEY
DOI: 10.1002/cncr.23904
Keywords
human embryonic lethal abnormal vision-like protein; cyclooxygenase-2; mesothelioma; prognosis; immunohistochemistry
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Funding
- FUTURA-Onlus
- Associazione Italiana per la Ricerca sol Cancro
- Ministry of Health, Ministry of University
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BACKGROUND. 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). METHODS. 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. RESULTS. 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). CONCLUSIONS. 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 Hull may have a potential clinical benefit in mesothelioma. Cancer 2008; 113:2761-9. (C) 2008 American Cancer Society.
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