Cyclooxygenase-1 Is Overexpressed in Multiple Genetically Engineered Mouse Models of Epithelial Ovarian Cancer

Takiko Daikoku, Susanne Tranguch, Irina N. Trofimova, Daniela M. Dinulescu, Tyler Jacks, Alexander Yu. Nikitin, Denise C. Connolly, Sudhansu K. Dey
2006 Cancer Research  
Cyclooxygenases-1 and -2 (Cox-1 and Cox-2) are two distinct isoforms that catalyze the conversion of arachidonic acid to prostaglandins. The role of Cox-2 in a variety of cancers is well recognized, but the contribution of Cox-1 remains much less explored. We have previously shown that human epithelial ovarian tumors have increased levels of Cox-1, but not Cox-2. We also observed that Cox-1 is highly expressed in a mouse model of epithelial ovarian cancer (EOC), which lacks p53 but
more » ... 53 but overexpresses c-myc and K-ras or c-myc and Akt. More importantly, a Cox-1-selective inhibitor, SC-560, attenuates EOC growth. In the present investigation, we used various genetically engineered mouse models of EOC to determine whether Cox-1 overexpression is unique to specific genetic and oncogenic alterations or is widespread. These models include: (a) deletion of both p53 and Rb, (b) induction of the transforming region of SV40 under the control of Mullerian inhibitory substance type II receptor, or (c) activation of K-Ras in the absence of Pten locally in the ovarian surface epithelium. We found that these three models, which produce spontaneous EOC, also show up-regulated expression of Cox-1, but not Cox-2. The results provide further evidence that Cox-1 overexpression is common in various models of EOC. Thus, Cox-1 serves as a potential marker of EOC and is a possible target for the prevention and/or treatment of this deadly disease.
doi:10.1158/0008-5472.can-05-4063 pmid:16510568 fatcat:sb6nvgwahbfixcplghwaoqgk6a