Oncotarget

Research Papers:

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

Andrew J. Wilson _, Oluwole Fadare, Alicia Beeghly-Fadiel, Deok-Soo Son, Qi Liu, Shilin Zhao, Jeanette Saskowski, Md. Jashim Uddin, Cristina Daniel, Brenda Crews, Brian D. Lehmann, Jennifer A. Pietenpol, Marta A. Crispens, Lawrence J. Marnett and Dineo Khabele

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Oncotarget. 2015; 6:21353-21368. https://doi.org/10.18632/oncotarget.3860

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Abstract

Andrew J. Wilson1, Oluwole Fadare2, Alicia Beeghly-Fadiel3,4, Deok-Soo Son5, Qi Liu6,7, Shilin Zhao7, Jeanette Saskowski1, Md. Jashim Uddin8,9, Cristina Daniel8,9, Brenda Crews8,9, Brian D. Lehmann4,8, Jennifer A. Pietenpol4,8, Marta A. Crispens1,4, Lawrence J. Marnett4,8,9, Dineo Khabele1,4

1Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN

2Department of Pathology, University of California San Diego School of Medicine, La Jolla, CA

3Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN

4Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN

5Department of Biochemistry & Cancer Biology, Meharry Medical College, Nashville, TN

6Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN

7Vanderbilt Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN

8Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN

9Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN

Correspondence to:

Dineo Khabele, e-mail: dineo.khabele@vanderbilt.edu

Keywords: high-grade serous ovarian cancer, cyclooxygenase-1, cell migration/invasion, pro-tumorigenic pathways

Received: February 25, 2015     Accepted: April 21, 2015     Published: May 04, 2015

ABSTRACT

Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.


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