Analyses of regulatory mechanisms in endometrial apoptosis

本研究利用自行建立的人子宫内膜上皮细胞系的体外培养系统，对人子宫内膜上皮细胞凋亡的调控机制进行了研究。我们建立了人子宫内膜腺癌细胞体外培养体系，用抗Fas IgM抗体或抗癌药物刺激。使用该培养系统，检查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。例如，我们的分析表明，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，例如Fas-mediated apoptosis，但不调节p53依赖性细胞凋亡，例如抗癌药物诱导的细胞凋亡。众所周知，人类子宫内膜间质细胞会分化成对于胚胎着床至关重要的蜕膜细胞。我们建立了一个新的体外蜕膜化检测系统，并分析了蜕膜化的调控机制。因此，我们发现白血病抑制因子白细胞介素-11和抑瘤素M等细胞因子可以调节子宫内膜间质的活性。在这项研究中，我们最初发现了人子宫内膜间质细胞分化为G-CSF分泌细胞的另一种分化途径。此外，表皮生长因子，也被发现调节两种类型的分化途径的基质cells.We已经建立了一个新的实验系统，在抗癌药物诱导的子宫内膜腺癌细胞凋亡的凋亡信号受损，并正在调查抗癌药物的损害。

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.