E-cadherin expression in ovarian cancer in the laying hen, Gallus domesticus, compared to human ovarian cancer

Abstract

Objective-Epithelial ovarian carcinoma (EOC) is a leading cause of cancer deaths in women. Until recently, a significant lack of an appropriate animal model has hindered the discovery of early detection markers for ovarian cancer. The aging hen serves as an animal model because it spontaneously develops ovarian adenocarcinomas similar in histological appearance to the human disease. E-cadherin is an adherens protein that is down-regulated in many cancers, but has been shown to be up-regulated in primary human ovarian cancer. Our objective was to evaluate E-cadherin expression in the hen ovary and compare its expression to human ovarian cancer. Methods-WhiteLeghorn hens aged 185 weeks (cancerous and normal) were used for sample collection. A human ovarian tumor tissue array was used for comparison to the human disease. Ecadherin mRNA and protein expression were analyzed in cancerous and normal hen ovaries by immunohistochemistry (IHC), Western blot, and quantitative real-time PCR (qRT-PCR). Tissue fixed in neutral buffered formalin was used for IHC. Protein from tissue frozen in liquid nitrogen was analyzed by Western blot. RNA was extracted from tissue preserved in RNAlater and analyzed by qRT-PCR. The human ovarian tumor tissue array was used for IHC.Results-E-cadherin mRNA and protein expression were significantly increased in cancerous hen ovaries as compared to ovaries of normal hens by qRT-PCR and Western blot. Similar expression of E-cadherin was observed by IHC in both human and hen ovarian cancer tissues. Similar E-cadherin expression was also observed in primary ovarian tumor and peritoneal metastatic tissue from cancerous hens.Conclusions-Our findings suggest that the up-regulation of E-cadherin is an early defining event in ovarian cancer and may play a significant role in the initial development of the primary ovarian tumor. E-cadherin also appears to be important in the development of secondary tumors within the peritoneal cavity. Our data suggest that E-cadherin may prove to be an important target in the preventative treatment of metastatic ovarian cancer and further confirm that the laying hen is a good model for the study of human epithelial ovarian carcinoma.

Gene Expression Profiling Reveals Differentially Expressed Genes in Ovarian Cancer of the Hen: Support for Oviductal Origin?

“…Our results support previous studies in the hen which reported increased expression of ovalbumin and E-cadherin in chicken ovarian tumors [8,38]. Ovalbumin and Ecadherin are in the list of the top 25 up-regulated genes in ovarian tumor tissue compared with normal ovarian tissue with expression levels increased >200-fold and 40-fold, respectively (Supplementary Table 1).…”

“…Hens have a high incidence of ovarian cancer and, similar to women, this incidence increases with age [3]. Several studies have reported that ovarian tumors of the hens express antigens that are frequently expressed in human ovarian tumors including cytokeratin, EGFR, HER-2/neu, COX-1, VEGF, and E-cadherin [4][5][6][7][8][9]. Barua et al found that chicken tumors resemble all four phenotypes found in women, with serous and endometrioid tumors present at about equal frequencies [10].…”

Uncovering molecular events associated with the chemosuppressive effects of flaxseed: a microarray analysis of the laying hen model of ovarian cancer

“…This E-cadherin pattern could potentially have diagnostic value, but more importantly, identifying factors that regulate E-cadherin expression in the ovary may give clues as to which pathways become dysregulated very early on during the transformation of normal cells toward a malignant phenotype. We have shown previously that E-cadherin is significantly upregulated in hen ovarian cancer similar to what is observed in the human disease [12]. qPCR analysis from the current study reveals that E-cadherin mRNA is decreased more than 40% in tumors from hens fed flaxseed (Figure  5) and E-cadherin protein has been shown to be decreased by 50% in tumors from flax-fed hens [22].…”

Advantages of the avian model for human ovarian cancer

“…Moreover, the sequencing of the chicken genome 10 years ago enabled valuable molecular comparisons with human cases (71). Different biomarkers, such as CA-125, P53 and E-cadherin, were also expressed in EOC in both species (28,(72)(73)(74).…”