60S acidic ribosomal protein P1 and endometriosis pathogenesis

项目摘要 子宫内膜异位症是一种严重影响全球7000万妇女的疾病。定义为异类 子宫内膜组织(腺体和间质)的生长，这种疾病影响年轻女孩和 妇女的生活质量下降，影响了她们的教育和职业生涯。子宫内膜异位症的主要治疗方法 依赖于减少雌激素的产生和/或作用。这种疗法并不是对所有女性都有效，它并不是 耐受性好，并与不想要的和潜在危害健康的副作用有关。因此， 对于这种常见的、使人虚弱的疾病，显然有必要确定新的、节省雌激素的治疗方法。 疾病。 我们成功治疗子宫内膜异位症的能力受到我们不完全理解的阻碍 关于这种疾病的发病机制。除了子宫内膜异位症是一种雌激素依赖型疾病之外， 病变存活、疼痛和不孕不育的确切媒介在很大程度上是未知的。在此应用程序中，我们报告 60S酸性核糖体蛋白P1在子宫内膜异位症中首次显著过度表达 将病变组织与同一患者的在位内膜以及对照组的在位内膜进行比较。RPLP1 在蛋白质合成中起着重要作用，其在多种癌症中的过度表达已被检测到 与细胞转化、增殖和侵袭有关的细胞类型。我们建议在 此授权应用程序在我们最初发现的基础上进行扩展，并测试RPLP1在 人子宫内膜异位病变组织可提高病变存活率。首先，我们将定义模式和细胞 RPLP1在子宫内膜异位症和配对子宫内膜组织中的定位 RPLP1过度表达与活体/增生性子宫内膜异位症相关的人群 病变组织。其次，我们将使用一种新的方法/动物模型来研究子宫内膜异位症 RPLP1在病变存活中的功能作用。最后，我们将确定RPLP1的下游目标，这些目标可能 代表了治疗子宫内膜异位症的新的、非激素靶点。 这项研究将为子宫内膜异位症领域提供新的知识，识别一种新的信号转导 与子宫内膜异位症发病机制相关的途径。这项研究的长期效益将增强 我们对子宫内膜异位症的认识，有可能改善女性的健康。成果来自于 这项拟议的研究有可能改变子宫内膜异位症的治疗方式，并可能提供新的 选择。

Project Summary Endometriosis is a significant disease which affects over 70 million women globally. Defined as ectopic growth of endometrial tissue (glands and stroma), this disease impacts the daily lives of young girls and women reducing their quality of life, impacting their education, and careers. Endometriosis treatment primarily relies on reduction of estrogen production and/or action. This treatment is not effective in all women, it is not well-tolerated and it is associated with unwanted and potentially health-compromising side effects. As such, there is a clear need for the identification of novel, estrogen-sparing treatments for this common, debilitating disease. Limitations in our ability to successfully treat endometriosis are hindered by our incomplete understanding on the pathogenesis of the disease. Beyond the fact the endometriosis is an estrogen-dependent disease the precise mediators of lesion survival, pain and infertility are largely unknown. In this application we report for the first time that the 60S acidic ribosomal protein P1 (RPLP1) is significantly over-expressed in endometriotic lesion tissue compared to eutopic endometrium from the same patient as well as from control subjects. RPLP1 plays an important role in protein synthesis and its over-expression has been detected in a variety of cancer cell types where it has been associated with cellular transformation, proliferation and invasion. We propose in this grant application to expand upon our initial findings and test the hypothesis that RPLP1 over-expression in human endometriotic lesion tissue enhances lesion survival. First, we will define the pattern and cellular localization of RPLP1 in endometriotic and paired endometrial tissue in a large, well characterized patient population demonstrating that RPLP1 over-expression is associated with viable/proliferating endometriotic lesion tissue. Secondly, we will use a novel approach/animal model for endometriosis to demonstrate the functional role of RPLP1 in lesion survival. Lastly, we will identify downstream targets of RPLP1 which may represent novel, non-hormonal targets for endometriosis treatment. The proposed research will provide new knowledge in field of endometriosis identifying a novel signaling pathways relevant to the pathogenesis of endometriosis. The long-term benefits of this research will enhance our understanding on the disease endometriosis and potentially improve women's health. The outcomes from the proposed research have the potential to change the way endometriosis may be treated and may offer new options.