ERAS抑制细胞凋亡作用的分子机理研究

Eras is a Ras family member that's highly expressed in early embryonic cells, besides which Eras can also be expressed in gastric cancer cells. In a family, we found two aborted male fetuses from the same mother carried a same Eras mutation. With medical genetic analysis, we excluded other mutations and assigned the Eras mutation to be the likely cause of the early miscarriage. The cell culture of villi cells revealed that the Eras mutation might lead to the slower cell growth and more apoptosis. Because of the limitation of primary cell culture, we propose to use gastric cancer cell lines as a model to study the ant-apoptotic mechanism of Eras. Key scientific questions: 1) In gastric cancer cells, what is the anti-apoptotic mechanism of Eras? 2) In a mouse model, how does Eras regulate the embryonic cells' apoptosis and how does the Eras mutation cause abortion? In summary, we will study the anti-apoptotic role of Eras in cell level and in animal level to revel the relationship between apoptosis and abortion.

ERas是Ras家族在早期胚胎发育中表达的一个管家基因，该基因也可在部分胃癌细胞系里表达。 在一个家系中，我们发现两例流产同母男婴都携带同一个ERas突变。通过医学遗传学分析，我们排除了其他变异，认为Eras突变可能是早期的胚胎停止发育的原因。通过对流产胎儿绒毛细胞的培养，我们发现携带ERas突变的绒毛细胞生长较缓慢，表现出更多的细胞凋亡特性。由于原代细胞培养的局限性，我们拟利用人的胃癌细胞为模型，来研究ERas在细胞凋亡中的作用机理。关键科学问题：1）在胃癌细胞系中，Eras调节细胞凋亡的作用机理；2）在小鼠模型中，ERas对胚胎细胞凋亡途径的调控机理以及其引起流产的原因探讨。总之，我们将在细胞水平和动物模型水平上，研究ERas的功能以及其突变体在细胞凋亡中的作用，并进一步揭示细胞凋亡和流产的关系。