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Analyses of regulatory mechanisms in endometrial apoptosis

子宫内膜细胞凋亡调控机制分析

基本信息

批准号：
10470347
负责人：
OGITA Sachio
金额：
$ 8.32万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

In this study, we analyzed regulatory mechanisms in human endometrial apoptosis by using in vitro culture system we developed originally.Experimental analyses of endometrial epithelial apoptosis were performed with a novel experimental apoptotic system of human endometrial epithelial cell lines. We developed the experimental culture system of the human endometrial adenocarcinoma stimulated with anti-Fas IgM antibody or anticancer drugs. Using the culture system, regulation of the apoptosis by various cytokines extracellular matrices, hormones or anticancer drugs were examined. Our analysis, for example, revealed that signals by extracellular matrices on endometrial epithelial cells regulated p53-independent apoptosis such as Fas-mediated apoptosis but not p53-dependent apoptosis such as anticancer drug-induced apoptosis.Human endometrial stromal cells are well known to differentiate into decidual cells that are essential to embryo implantation. We established a novel in vitro decidualization assay system and analyzed regulatory mechanisms of decidualization. As a result, we have found several cytokines such as leukemia inhibitory factor interleukin-11 and oncostatin M can regulate endometrial stromal viability. In the study, we have originally discovered another differentiation pathway of human endometrial stromal cells that differentiate to G-CSF-secreting cells. Epidermal growth factor, moreover, is also found to regulate the two types of differentiation pathways of the stromal cells.We have established a novel experimental system of impaired apoptotic signals in anticancer-drug-induced apoptosis in endometrial adenocarcinoma cells and are under investigation of impairment of anticancer-drug.

本研究利用自行研制的体外培养系统，对人子宫内膜上皮细胞凋亡的调控机制进行了研究，并利用一种新的人子宫内膜上皮细胞株的实验凋亡系统进行了子宫内膜上皮细胞凋亡的实验研究。我们建立了抗Fas-IgM抗体或抗癌药物刺激的人子宫内膜腺癌细胞的实验培养体系。利用该培养体系，检测了不同细胞因子、细胞外基质、激素或抗癌药物对细胞凋亡的调节作用。例如，我们的分析显示，子宫内膜上皮细胞上的细胞外基质信号调节P53非依赖性的细胞凋亡，如Fas介导的凋亡，但不调控P53依赖的细胞凋亡，如抗癌药物诱导的凋亡。众所周知，人子宫内膜基质细胞分化为对胚胎植入至关重要的蜕膜细胞。我们建立了一种新的体外蜕膜化检测系统，并对蜕膜化的调控机制进行了分析。因此，我们发现一些细胞因子如白血病抑制因子IL-11和抑癌素M可以调节子宫内膜间质的活性。在这项研究中，我们首次发现了人子宫内膜间质细胞分化为G-CSF分泌细胞的另一条分化途径。此外，还发现表皮生长因子还调节间质细胞的两种分化途径。我们建立了一个新的抗癌药物诱导子宫内膜腺癌细胞凋亡信号受损的实验系统，并正在研究抗癌药物的损伤。