Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease

Abstract

Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due, in part, to the lack of early detection methods and incomplete understanding of the origin of the disease. Animal models of ovarian cancer can shed light on the genetic and biological factors that influence tumor development and/or progression, as well as identify strategies for prevention, early detection and treatment. One animal model, the domestic hen, has a high spontaneous incidence of the disease that is age-dependent, similar to women. Although previous studies utilizing the hen as a model for ovarian cancer have characterized chicken ovarian tumors and tested putative prevention and treatment strategies of the disease, our understanding of the development and progression of ovarian cancer in the hen is still limited. Our objectives were 1) to further characterize chicken ovarian tumors through global gene expression analysis; 2) to test the effect of progestin and estrogen together, as commonly delivered in "the pill", as well as progestin and estrogen alone on ovarian cancer prevalence in the hen; and 3) to determine estrogen receptor subtype expression in chicken ovarian tumors. The second and third objectives were based on evidence in women that steroid hormones play a role in ovarian cancer, with estrogen associated with an increased risk and progesterone associated with a decreased risk of the disease. We have shown that administration of "the pill" is associated with a significant decrease in ovarian cancer prevalence, as well as egg production, suggesting that ovulation is important for the initiation of ovarian cancer. Furthermore, we observed that chicken ovarian tumors over-express oviduct-related genes, even at early stages, providing evidence that tumors possibly arise from the epithelial cells of the oviduct. Finally, our results also support a role for steroid hormones, particularly estrogen, in mediating ovarian tumor progression. Collectively, our studies have provided information regarding the development and progression of ovarian cancer in the hen that may help unlock the mysteries of the disease in women.