title: Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer.
abstract: 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 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.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: Takiko
authors.initials: T
authors.lastname: Daikoku
authors.forename: Susanne
authors.initials: S
authors.lastname: Tranguch
authors.forename: Irina N
authors.initials: IN
authors.lastname: Trofimova
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Dinulescu
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Nikitin
authors.forename: Denise C
authors.initials: DC
authors.lastname: Connolly
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000096:biosynthesis / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics
chemical_list: D000952:Antigens, Polyomavirus Transforming; D051545:Cyclooxygenase 1