This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Erkinheimo, T.-L. Articles by Ristimäki, A. Search for Related Content PubMed PubMed Citation Articles by Erkinheimo, T.-L. Articles by Ristimäki, A.

Cytoplasmic HuR Expression Correlates with Poor Outcome and with Cyclooxygenase 2 Expression in Serous Ovarian Carcinoma

Departments of
¹ Gynecology and Obstetrics,
² Pathology,
³ Surgery, Helsinki University Central Hospital, Helsinki, Finland;
⁴ Molecular and Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland;
⁵ Center for Vascular Biology, Departments of Biochemistry
⁶ Physiology, University of Connecticut Health Center, Farmington, Connecticut

Cyclooxygenase-2 (COX-2) expression has been shown to associate with poor prognosis in ovarian cancer, and an mRNA stability protein HuR has been shown to enhance expression of COX-2 in tissue culture conditions. We found cytoplasmic immunoreactivity for HuR protein in 52% (233 of 445) of serous-type ovarian carcinoma specimens, and it associated with high COX-2 expression (P = 0.0045) and with clinicopathological variables, including poor prognosis (P < 0.0001) and high grade (P < 0.0001). In ovarian cancer cells in vitro, a small interfering RNA against HuR and leptomycin B, an inhibitor of nucleocytoplasmic translocation of HuR, inhibited COX-2 expression. Our results show that cytoplasmic HuR expression associates with poor outcome in ovarian cancer, and one plausible explanation for this finding may be related to the ability of HuR to induce COX-2 expression.

This article has been cited by other articles:

				I. Lopez de Silanes, M. Gorospe, H. Taniguchi, K. Abdelmohsen, S. Srikantan, M. Alaminos, M. Berdasco, R. G. Urdinguio, M. F. Fraga, F. V. Jacinto, et al. The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA Nucleic Acids Res., May 1, 2009; 37(8): 2658 - 2671. [Abstract] [Full Text] [PDF]

				J. M. Saunus, J. D. French, S. L. Edwards, D. J. Beveridge, E. C. Hatchell, S. A. Wagner, S. R. Stein, A. Davidson, K. J. Simpson, G. D. Francis, et al. Posttranscriptional Regulation of the Breast Cancer Susceptibility Gene BRCA1 by the RNA Binding Protein HuR Cancer Res., November 15, 2008; 68(22): 9469 - 9478. [Abstract] [Full Text] [PDF]

				A. D. Ortega, S. Sala, E. Espinosa, M. Gonzalez-Baron, and J. M. Cuezva HuR and the bioenergetic signature of breast cancer: a low tumor expression of the RNA-binding protein predicts a higher risk of disease recurrence Carcinogenesis, November 1, 2008; 29(11): 2053 - 2061. [Abstract] [Full Text] [PDF]

				R. A. Oyesanya, Z. P. Lee, J. Wu, J. Chen, Y. Song, A. Mukherjee, P. Dent, T. Kordula, H. Zhou, and X. Fang Transcriptional and post-transcriptional mechanisms for lysophosphatidic acid-induced cyclooxygenase-2 expression in ovarian cancer cells FASEB J, August 1, 2008; 22(8): 2639 - 2651. [Abstract] [Full Text] [PDF]

				C. L. Kanies, J. J. Smith, C. Kis, C. Schmidt, S. Levy, K. S.A. Khabar, J. Morrow, N. Deane, D. A. Dixon, and R. D. Beauchamp Oncogenic Ras and Transforming Growth Factor-{beta} Synergistically Regulate AU-Rich Element-Containing mRNAs during Epithelial to Mesenchymal Transition Mol. Cancer Res., July 1, 2008; 6(7): 1124 - 1136. [Abstract] [Full Text] [PDF]

				A. Doller, E.-S. Akool, A. Huwiler, R. Muller, H. H. Radeke, J. Pfeilschifter, and W. Eberhardt Posttranslational Modification of the AU-Rich Element Binding Protein HuR by Protein Kinase C{delta} Elicits Angiotensin II-Induced Stabilization and Nuclear Export of Cyclooxygenase 2 mRNA Mol. Cell. Biol., April 15, 2008; 28(8): 2608 - 2625. [Abstract] [Full Text] [PDF]

				M. Heinonen, R. Fagerholm, K. Aaltonen, O. Kilpivaara, K. Aittomaki, C. Blomqvist, P. Heikkila, C. Haglund, H. Nevanlinna, and A. Ristimaki Prognostic Role of HuR in Hereditary Breast Cancer Clin. Cancer Res., December 1, 2007; 13(23): 6959 - 6963. [Abstract] [Full Text] [PDF]

				K. Leandersson, K. Riesbeck, and T. Andersson Wnt-5a mRNA translation is suppressed by the Elav-like protein HuR in human breast epithelial cells Nucleic Acids Res., September 1, 2006; 34(14): 3988 - 3999. [Abstract] [Full Text] [PDF]

				J. Mrena, J.-P. Wiksten, A. Thiel, A. Kokkola, L. Pohjola, J. Lundin, S. Nordling, A. Ristimaki, and C. Haglund Cyclooxygenase-2 Is an Independent Prognostic Factor in Gastric Cancer and Its Expression Is Regulated by the Messenger RNA Stability Factor HuR Clin. Cancer Res., October 15, 2005; 11(20): 7362 - 7368. [Abstract] [Full Text] [PDF]

				T. Daikoku, D. Wang, S. Tranguch, J. D. Morrow, S. Orsulic, R. N. DuBois, and S. K. Dey Cyclooxygenase-1 Is a Potential Target for Prevention and Treatment of Ovarian Epithelial Cancer Cancer Res., May 1, 2005; 65(9): 3735 - 3744. [Abstract] [Full Text] [PDF]

				M. Heinonen, P. Bono, K. Narko, S.-H. Chang, J. Lundin, H. Joensuu, H. Furneaux, T. Hla, C. Haglund, and A. Ristimaki Cytoplasmic HuR Expression Is a Prognostic Factor in Invasive Ductal Breast Carcinoma Cancer Res., March 15, 2005; 65(6): 2157 - 2161. [Abstract] [Full Text] [PDF]

				C. Denkert, W. Weichert, K.-J. Winzer, B.-M. Muller, A. Noske, S. Niesporek, G. Kristiansen, H. Guski, M. Dietel, and S. Hauptmann Expression of the ELAV-Like Protein HuR Is Associated with Higher Tumor Grade and Increased Cyclooxygenase-2 Expression in Human Breast Carcinoma Clin. Cancer Res., August 15, 2004; 10(16): 5580 - 5586. [Abstract] [Full Text] [PDF]

				F. Spinella, L. Rosano, V. Di Castro, M. R. Nicotra, P. G. Natali, and A. Bagnato Inhibition of Cyclooxygenase-1 and -2 Expression by Targeting the Endothelin A Receptor in Human Ovarian Carcinoma Cells Clin. Cancer Res., July 15, 2004; 10(14): 4670 - 4679. [Abstract] [Full Text] [PDF]