Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma

Association with cyclooxygenase-2 and prognosis

Authors

  • Daniela Stoppoloni BSC,

    1. Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy
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  • Irene Cardillo BSC,

    1. Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy
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  • Alessandra Verdina BSC,

    1. Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy
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  • Bruno Vincenzi MD,

    1. Section of Oncology, Campus BioMedico University, Rome, Italy
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  • Simona Menegozzo MD,

    1. Campania Regional Operating Center of the National Mesothelioma Registry and Department of Experimental Medicine, Second University of Naples, Naples, Italy
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  • Mario Santini MD,

    1. Department of Thoracic Surgery, Second University of Naples, Naples, Italy
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  • Ada Sacchi BSC,

    1. Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy
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  • Alfonso Baldi MD,

    Corresponding author
    1. Section of Anatomic Pathology, Department of Biochemistry and Biophysic “F. Cedrangolo,” Second University of Naples, Naples, Italy
    • Section of Anatomic Pathology, Department of Biochemistry and Biophysic “F. Cedrangolo,” Second University of Naples, Via L. Armanni 5, 80138 Naples, Italy===

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    • Fax: (011) 390815569693

  • Rossella Galati BSC

    1. Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy
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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. Cancer 2008. © 2008 American Cancer Society.

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