Expression of the embryonic lethal abnormal vision-like protein HuR in human mesothelioma: association with cyclooxygenase-2 and prognosis.
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.
Stoppoloni
Daniela
D
Laboratory D, Department for the Development of Therapeutic Programs, Centro Ricerca Sperimentale, Regina Elena Cancer Institute, Rome, Italy.
Cardillo
Irene
I
Verdina
Alessandra
A
Vincenzi
Bruno
B
Menegozzo
Simona
S
Santini
Mario
M
Sacchi
Ada
A
Baldi
Alfonso
A
Galati
Rossella
R
D000954:Antigens, Surface / Q000096:biosynthesis* / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008654:Mesothelioma / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D016207:Cytokines; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2