Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer.
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.
Daikoku
Takiko
T
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Tranguch
Susanne
S
Trofimova
Irina N
IN
Dinulescu
Daniela M
DM
Jacks
Tyler
T
Nikitin
Alexander Yu
AY
Connolly
Denise C
DC
Dey
Sudhansu K
SK
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
D000952:Antigens, Polyomavirus Transforming; D051545:Cyclooxygenase 1