Role of estrogen and its receptors in ovarian cancer of the hen

描述（由申请人提供）：项目摘要：卵巢癌是妇女癌症死亡的第五大原因。众所周知，接受纯雌激素替代疗法的女性患卵巢癌的风险会增加，而服用避孕药的女性患卵巢癌的风险可能会降低，这为类固醇激素在卵巢癌病因中发挥作用的观点提供了支持。本课题旨在阐明雌激素及其受体在家鸡卵巢癌中的作用。母鸡是一个很好的模型，因为它患卵巢癌的自发性发病率很高。本研究的具体目的是：1)确定母鸡的卵巢癌是否依赖雌激素；2)确定雌激素受体在卵巢癌中是否存在差异调节；3)表征非核雌激素受体；4)确定与雌激素受体介导的增殖相关的下游通路。这些问题将通过多种分子技术得到解答，包括PCR、Western blot、免疫组织化学和微阵列分析、体外方法（包括细胞培养）、体外（或蛋内）方法（包括正常和肿瘤卵巢组织的CAM移植）以及体内方法（包括用雌二醇治疗母鸡）。一旦这些问题得到解答，我们将对雌激素及其受体在卵巢癌中的作用有更好的了解。这些答案也将使我们了解雌激素作用促进母鸡卵巢肿瘤形成或增殖的机制，这可能与雌激素及其受体在人类卵巢癌中的作用有关。此外，了解雌激素的作用可能会导致可能适用于人类疾病的治疗方案。相关性：卵巢癌是妇女癌症死亡的第五大原因。雌激素可能促进卵巢肿瘤的发生或增殖；因此，了解其在疾病起源或进展中的作用是很重要的。

DESCRIPTION (provided by applicant): Project summary: Ovarian cancer is the fifth leading cause of cancer death among women. It is known that there is an increased risk of ovarian cancer in women who are on estrogen-only hormone replacement therapy and possible decreased risk in women who take the contraceptive pill, lending support to the idea that steroid hormones are playing a role in the etiology of ovarian cancer. This project is designed to clarify the role of estrogen and its receptors in ovarian cancer of the domestic hen. The hen is a good model because it develops ovarian cancer with a high spontaneous incidence. The specific aims of this study are to: 1) determine whether ovarian cancer in the hen is estrogen dependent; 2) determine if the estrogen receptor is differentially regulated in ovarian cancer; 3) characterize the non-nuclear estrogen receptor; and 4) determine downstream pathways associated with estrogen receptor mediated proliferation. These questions will be answered using a variety of molecular techniques including PCR, Western blot, immunohistochemistry and microarray analyses, in vitro methods including cell culture, ex vivo (or in ovo) methods including CAM grafts of normal and tumor ovarian tissue, and in vivo methods including treatment of hens with estradiol. Once these questions are answered, we will have a better understanding of the role of estrogen and its receptors in ovarian cancer. These answers will also allow us to understand the mechanism of estrogen action promoting the formation or proliferation of ovarian tumors in the hen, which may be correlated to the role estrogen and its receptors may play in human ovarian cancer. Furthermore, understanding estrogen's actions might lead to possible treatment options that could be applicable to human disease. Relevance: Ovarian cancer is the fifth leading cause of cancer death among women. Estrogens may promote ovarian tumor initiation or proliferation; therefore, it is important to understand its role in the origin or progression of the disease.