Age dependent increase in prostaglandin pathway coincides with onset of ovarian cancer in laying hens

Abstract

Chronic inflammation has been linked to cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory lipid and one of the downstream products of 2 isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Ovarian cancer is the most lethal gynecological malignancy and mainly occurs in older women. The factors that contribute to the correlation of age and ovarian cancer are unknown. The purpose of this study was to examine the expression of COX enzymes and PGE2 levels in ovaries and correlate them to ovarian cancer and aging. White Leghorn hens aged 1, 1.5, 2, 2.5, 3 and 3.5 years were used. The incidence of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 protein and mRNA expression and PGE2 concentrations in ovaries were measured using Western blot, quantitative real-time PCR and ELISA, respectively. Our results indicated an increase in ovarian cancer incidence and expression of both COX enzymes in ovaries of older hens. In correlation with ovarian cancer incidence and COX enzymes expression, PGE2 concentrations were elevated with age. Ovaries with tumor had elevated COX-1 expression and PGE2 concentration compared to normal ovaries. Our findings suggest that the up-regulation of COX enzymes with age is the main contributing factor in the age associated increase in PGE2. Furthermore, elevated PGE2 in ovaries of hens concomitant with age suggests its important role in early stages of ovarian carcinogenesis. These finding may provide the basis for clinical trials utilizing COX specific inhibitors or dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

“…Blood was collected at different time points throughout the study by wing vein puncture and tissues were harvested at the end of the study after sacrificing the hens. Tissue collection and processing was done as described previously [34]. …”

“…Total RNA was extracted from ovarian tissue using Trizol reagent as described previously [34, 35]. RNA was quantified by measuring the sample absorbance at A260.…”

“…Proteins were isolated from the ovary samples as described previously [34]. Twenty five micrograms of total protein was separated using a SDS-PAGE gel with 10% acrylamide/SDS separating gels and transferred to nitrocellulose membranes.…”

Preclinical Models of Ovarian Cancer: Pathogenesis, Problems, and Implications for Prevention

“…60 The incidence increases to 30–60% after 4–6 years. 61, 62 The hens develop ovarian tumors with peritoneal spread and ascites, similar to women with advanced-stage disease. Four histotypes of ovarian cancer have been described: HGSC, EC, CCC and MC.…”

Aspects immunologiques du cancer de l’ovaire : perspectives thérapeutiques

“…Ces effets sont bloqués par les inhibiteurs de COX2, mais la participation du système immunitaire n'est pas prouvée puisque dans ce système, les métalloprotéases MMP-2 et MMP-9, acteurs dans l'invasion et le développe-ment des métastases qui interviennent [170]. Le pic de concentration de PGE 2 dans les ovaires de poules correspond à l'âge de la plus grande prévalence des cancers de l'ovaire [171]. Les effets sur l'agressivité des cancers de l'ovaire des molécules adrénergiques passeraient par l'augmentation de la synthèse de PGE2.…”