Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma: Association with cyclooxygenase-2 and prognosis

Daniela Stoppoloni, Irene Cardillo, Alessandra Verdina, Bruno Vincenzi, Simona Menegozzo, Mario Santini, Ada Sacchi, Alfonso Baldi, Rossella Galati

Research output: Contribution to journalArticle

Abstract

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 HuR may have a potential clinical benefit in mesothelioma.

Original languageEnglish
Pages (from-to)2761-2769
Number of pages9
JournalCancer
Volume113
Issue number10
DOIs
Publication statusPublished - Nov 15 2008

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Keywords

  • Cyclooxygenase-2
  • Human embryonic lethal abnormal vision-like protein
  • Immunohistochemistry
  • Mesothelioma
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Stoppoloni, D., Cardillo, I., Verdina, A., Vincenzi, B., Menegozzo, S., Santini, M., Sacchi, A., Baldi, A., & Galati, R. (2008). Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma: Association with cyclooxygenase-2 and prognosis. Cancer, 113(10), 2761-2769. https://doi.org/10.1002/cncr.23904