BIOLOGY OF THE PRIMATE OVARIAN SURFACE EPITHELIUM

灵长类动物卵巢表面上皮的生物学

• 批准号: 8357773
• 负责人: Jay W Wright
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357773
• 关键词: Biological Models; Biology; Cadherins; Data; E-Cadherin; Epithelial ovarian cancer; Epithelium; Estrogens; Etiology; Funding; Grant; Health; Human; Macaca; Macaca mulatta; Malignant neoplasm of ovary; Menstrual cycle; Methods; Modeling; National Center for Research Resources; Ovarian; Ovulation; Phase; Primates; Principal Investigator; Progesterone; Protein Isoforms; Research; Research Infrastructure; Resources; Risk; Role; Source; Surface; United States National Institutes of Health; Woman; base; cancer therapy; cost; in vivo; nonhuman primate; novel strategies; novel therapeutics; ovarian cancer prevention; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The etiology of epithelial ovarian cancer (EOC)is poorly understood. The ovarian surface epithelium (OSE), the source of EOC in women, has not been effectively studied, which has limited progress in developing strategies for EOC treatment. Due to the infeasibility of human studies, we selected the rhesus monkey as an alternative model to study the OSE. The macaque is reproductively and genetically similar to women, and EOC occurs in other nonhuman primates, but not nonprimates. Our aims are to characterize the primate OSE at distinct phases of the menstrual cycle using immunohistochemical methods; to determine whether ovarian factors (estrogen and progesterone) dynamically regulate the OSE in vivo; and to establish whether the OSE is an essential component of ovarian function and health. This project will establish a fundamental baseline to understand the primate OSE and provide a model system for hypothesis-based experiments to evaluate risks for ovarian cancer and novel therapeutic strategies. We have demonstrated that the OSE is not required for ovulation. We also have generated preliminary data in fulfillment of grant aims, indicating that high levels of estrogen may stimulate proliferation in the OSE in vivo. We have performed immunhistochemical studies that identify E-cadherin as the predominant cadherin isoform expressed by OSE in vivo, and confirmed this is true in the OSE of women as well (in contrast to the findings of others). Because the primate OSE has no apparent role in ovulation, its elimination may provide a novel strategy for EOC prevention.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 上皮性卵巢癌（EOC）的病因学知之甚少。 卵巢表面上皮细胞（OSE）是女性EOC的来源，尚未得到有效研究，这限制了EOC治疗策略的发展。 由于人体研究的不可行性，我们选择恒河猴作为研究OSE的替代模型。猕猴在生殖和遗传上与女性相似，EOC发生在其他非人类灵长类动物中，但不是非灵长类动物。 我们的目的是表征灵长类动物OSE在月经周期的不同阶段，使用免疫组化方法，以确定是否卵巢因素（雌激素和孕激素）动态调节OSE在体内，并建立OSE是否是卵巢功能和健康的重要组成部分。 该项目将建立一个基本的基线，以了解灵长类动物OSE，并提供一个基于假设的实验模型系统，以评估卵巢癌的风险和新的治疗策略。我们已经证明OSE不是排卵所必需的。 我们也产生了初步的数据，在实现赠款的目标，表明高水平的雌激素可能会刺激增殖的OSE在体内。 我们已经进行了免疫组化研究，确定E-cadherin作为OSE在体内表达的主要钙粘蛋白亚型，并证实这在女性OSE中也是如此（与其他人的发现相反）。 由于灵长类动物OSE在排卵中没有明显的作用，因此消除它可能为EOC预防提供一种新的策略。