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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 上皮性卵巢癌（EOC）的病因尚不清楚。 卵巢表面上皮 (OSE) 作为女性 EOC 的来源，尚未得到有效研究，这限制了 EOC 治疗策略的制定进展。 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，但非灵长类动物中则不然。 我们的目标是使用免疫组织化学方法表征灵长类动物在月经周期不同阶段的 OSE；确定卵巢因子（雌激素和孕激素）是否动态调节体内 OSE；并确定 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基线来了解灵长类动物 OSE，并为基于假设的实验提供模型系统，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。 我们还生成了实现资助目标的初步数据，表明高水平的雌激素可能会刺激体内 OSE 的增殖。 我们进行了免疫组织化学研究，确定 E-钙粘蛋白是 OSE 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（与其他人的研究结果相反）。 由于灵长类动物 OSE 在排卵中没有明显作用，因此消除它可能为 EOC 预防提供新策略。