Analyses of regulatory mechanisms in endometrial apoptosis

在本研究中，我们利用自主研发的体外培养系统分析了人子宫内膜凋亡的调控机制。利用一种新的人子宫内膜上皮细胞凋亡实验系统对子宫内膜上皮细胞凋亡进行了实验分析。建立了用抗fas IgM抗体或抗癌药物刺激人子宫内膜腺癌的实验培养系统。利用培养系统，研究了各种细胞因子、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非依赖性细胞凋亡，如fas介导的细胞凋亡，但不调节p53依赖性细胞凋亡，如抗癌药物诱导的细胞凋亡。众所周知，人子宫内膜基质细胞可以分化为胚胎着床所必需的蜕膜细胞。我们建立了一种新的体外脱个体化检测系统，并分析了脱个体化的调控机制。因此，我们发现几种细胞因子如白血病抑制因子白介素-11和抑癌素M可以调节子宫内膜间质活力。在本研究中，我们首次发现了人子宫内膜基质细胞向g - csf分泌细胞分化的另一条分化途径。此外，还发现表皮生长因子调节基质细胞的两种分化途径。我们建立了抗癌药物诱导的子宫内膜腺癌细胞凋亡中凋亡信号受损的实验系统，并正在对抗癌药物的损伤进行研究。

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.