Abstract 4616: Age dependent increase in Prostaglandin pathway coincides with onset of ovarian cancer in laying hens

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL The link between chronic inflammation and cancer has been recognized for many years. Cyclooxygenase (COX) (PTGS) is the rate limiting enzyme in catalyzing the conversion of arachidonic acid to prostaglandins. Two isoforms of cyclooxygenase has been identified, COX-1 and COX-2. Ovarian cancer is the fifth leading cause of cancer death among women and the most lethal gynecological malignancy. Ovarian cancer is mainly seen in older women when their ovaries are not reproductively functional. Hens spontaneously develop ovarian adenocarcinomas that are similar in histological appearance to human ovarian carcinomas and share similar symptoms of the disease thus the laying hen is the only accessible animal model that recapitulates human ovarian cancer. Many hypotheses about etiology of ovarian cancer have been proposed but the factors that contribute to correlation of age and ovarian cancer are unknown. The purpose of this study was to examine the expression of inflammatory factors and compare them to age. White Leghorn hens aged 12-45 months were used. The incidence of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 mRNA were extracted from ovarian tissue, preserved in RNAlater and their expression was determined using quantitative real-time PCR (qRT-PCR). Protein of both COX enzymes was isolated from ovarian tissue frozen in liquid nitrogen and were analyzed by Western blot. Ovarian tissue fixed in neutral buffered formalin was used for histology. Prostaglandin E2 amounts was measured in frozen ovarian tissues using ELISA. A significant increase in the incidence of ovarian cancer with age in laying hen was detected. The expression of both COX-1 and COX-2 protein and mRNA was remarkably increased in older hens compared to younger hens. In correlation with increased ovarian cancer incidence, expression of both COX enzymes and PGE2 concentration were elevated significantly with age. Our finding suggests that the up-regulation of COX mRNA and protein levels with age is the main contributing factor in the age associated increase in prostaglandin E2. The present study provides the first insight into the age-related changes in the expression of COX-1, COX-2 and prostaglandin E2. The results of current study demonstrated that PGE2 was elevated in ovaries of hens concomitant with age indicating its possible role in initiation and/or progression of ovarian malignancies. These finding may provide the basis for clinical trials utilizing COX specific inhibitors or dietary intervention targeting prostaglandin biosynthesis for the treatment and prevention of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4616. doi:1538-7445.AM2012-4616