ROLE OF THE FAS ANTIGEN IN OVARIAN CELL APOPTOSIS

描述：（扫描自申请人摘要）拟定实验 将检验卵巢癌发生过程中细胞周期的改变 卵泡的发育调节卵泡细胞的敏感性， 凋亡这些变化影响卵泡发育的关键阶段 包括（1）选择优势卵泡发育至 排卵期和（2）终末分化的颗粒细胞后， 排卵前促黄体生成激素（LH）激增。我们以前的工作表明， 卵泡中存在功能性Fas抗原（Fas）通路。FAS 是一种细胞表面受体，结合后可诱导敏感细胞凋亡 Fas配体（FasL）。颗粒细胞和卵泡膜细胞同时表达Fas和FasL 并且表达随动情周期中卵泡发育而变化。的 Fas通路在卵巢细胞中高度调节，并受生长调节 因子和细胞因子。来自排卵前卵泡的牛颗粒细胞， 在体内暴露于LH峰变得对FasL诱导的和血清 戒断诱导的细胞凋亡。具体目标一是确定是否耐药 细胞凋亡是由以下因素介导的：A.细胞诱导的细胞周期退出 周期调节蛋白和/或B。孕酮受体的诱导， 随后孕酮受体介导的对细胞周期的影响。具体 目的二是探讨抑制FasL诱导的细胞凋亡的机制 牛颗粒细胞的生长因子。具体目标三： 调节细胞周期对颗粒细胞凋亡敏感性的影响 将被确定。具体目标IV是检验雌二醇 通过调节颗粒细胞的凋亡抑制FasL诱导的颗粒细胞凋亡 周期芳香化酶表达、细胞周期蛋白D2表达、 颗粒细胞增殖和逃避凋亡的选择过程中， 将确定主导卵泡。了解卵泡闭锁是 对于发展更好的生育控制方法至关重要， 治疗不孕症和提高生育能力。理解路径 促进或阻止卵巢细胞对凋亡的易感性可能导致 开发卵巢癌和其他癌症的新疗法。

DESCRIPTION: (Scanned from the applicant's abstract) The proposed experiments will test the hypothesis that alterations in the cell cycle during ovarian follicle development modulate the susceptibility of follicle cells to undergo apoptosis. These changes affect critical stages of follicle development including (1) selection of the dominant follicle for development to the ovulatory stage and (2) terminal differentiation of granulosa cells after the preovulatory luteinizing hormone (LH) surge. Our previous work demonstrated the presence of a functional Fas antigen (Fas) pathway in the ovarian follicle. Fas is a cell surface receptor that induces apoptosis in sensitive cells when bound by Fas ligand (FasL). Granulosa and theca cells can express both Fas and FasL and expression varies with follicle development during the estrous cycle. The Fas pathway is highly regulated in ovarian cells and is modulated by growth factors and cytokines. Bovine granulosa cells from preovulatory follicles that are exposed to an LH surge in vivo become resistant to FasL-induced and serum withdrawal-induced apoptosis. Specific aim I is to determine whether resistance to apoptosis is mediated by: A. Withdrawal from the cell cycle induced by cell cycle regulatory proteins and/or B. Induction of the progesterone receptor and subsequent progesterone receptor-mediated effects on the cell cycle. Specific aim II is to determine the mechanism for inhibition of FasL-induced apoptosis of bovine granulosa cells by growth factors. In specific aim III the effect of modulating the cell cycle on susceptibility of granulosa cells to apoptosis will be determined. Specific aim IV is to test the hypothesis that estradiol inhibits FasL-induced apoptosis of granulosa cells by modulating the cell cycle. Relationships among aromatase expression, cyclin D2 expression, granulosa cell proliferation and escape from apoptosis during selection of the dominant follicle will be determined. An understanding of follicle atresia is essential to allow development of improved methods of fertility control, treatment of infertility and enhancement of fertility. Understanding pathways that promote or prevent susceptibility of ovarian cells to apoptosis may lead to development of novel therapies for ovarian and other cancers.