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

Abstract

Ovarian cancer has a high mortality rate due, in part, to the lack of early detection and incomplete understanding of the origin of the disease. The hen is the only spontaneous model of ovarian cancer and can therefore aid in the identification and testing of early detection strategies and therapeutics. Our aim was to combine the use of the hen animal model and microarray technology to identify differentially expressed genes in ovarian tissue from normal hens compared with hens with ovarian cancer. We found that the transcripts up-regulated in chicken ovarian tumors were enriched for oviduct-related genes. Quantitative real-time PCR and immunohistochemistry confirmed expression of oviduct-related genes in normal oviduct and in ovaries from hens with early- and late-stage ovarian tumors, but not in normal ovarian surface epithelium. In addition, one of the oviduct-related genes identified in our analysis, paired box 2 has been implicated in human ovarian cancer and may serve as a marker of the disease. Furthermore, estrogen receptor 1 mRNA is over-expressed in early-stage tumors, suggesting that expression of the oviduct-related genes may be regulated by estrogen. We have also identified oviduct-related genes that encode secreted proteins that could represent putative serum biomarkers. The expression of oviduct-related genes in early-stage tumors is similar to what is seen in human ovarian cancer, with tumors resembling normal Müllerian epithelium. These data suggest that chicken ovarian tumors may arise from alternative sites, including the oviduct.

Differential expression of vitelline membrane outer layer protein 1: Hormonal regulation of expression in the oviduct and in ovarian carcinomas from laying hens

“…In accordance with previous studies, several oviduct-related genes are uniquely up-regulated in cancerous, but not normal ovaries from laying hens (Trevino et al, 2010). Therefore, we examined whether VMO1 expression changed during development of ovarian cancer in laying hens.…”

Advantages of the avian model for human ovarian cancer

“…In the hen, the expression of proteins that are specifically expressed in the oviduct during the later stages of the disease, such as ovoalbumin, ovostatin 2, PAX2 protein or EGFR1, indicate involvement of the oviduct in disease development (10,72). This finding supports the involvement of the Fallopian tube epithelium in spontaneous EOC, as in humans.…”

“…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).…”

Prostaglandin D2 synthase related to estrogen in the female reproductive tract

“…Epithelial cell-derived ovarian cancer (EOC) may arise from the distal oviduct of laying hens and many oviduct-associated genes are up-regulated in EOC by dysregulated estrogen levels [28]. Unfortunately, there are no or few symptoms and diagnostic biomarkers to detect early stage EOC in spite of the fact that it is the most common cause of cancer-related deaths among women [29,30].…”