脚手架蛋白NEDD9在宫颈癌细胞衰老中的作用及其分子机制

项目名称： 脚手架蛋白NEDD9在宫颈癌细胞衰老中的作用及其分子机制

项目编号： No.30801227

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 司马妮

作者单位： 浙江大学

项目金额： 20万元

中文摘要： 诱导肿瘤细胞衰老是一种治疗恶性肿瘤非常有前景和希望的方法，但目前肿瘤细胞衰老的机制尚未明了。我们在前期研究工作中利用表达谱芯片、蛋白印迹等技术发现神经前体细胞表达的发育下调基因9（NEDD9）可能参与宫颈癌细胞对细胞衰老的逃逸。本项目拟在前期研究的基础上，从临床组织、细胞、亚细胞、分子等多个水平，利用免疫共沉淀、RNA干扰、激光共聚焦、流式细胞术、衰老相关β21322;乳糖苷酶（Senescence-associated βal）活性检测等技术对NEDD9与宫颈癌细胞衰老进行相关研究，以明确NEDD9的表达水平及其酪氨酸磷酸化状态、亚细胞定位等对宫颈癌细胞衰老的影响，探讨NEDD9与细胞衰老相关蛋白的作用，从而证实NEDD9对宫颈癌细胞衰老的抑制作用，并探讨NEDD9调控宫颈癌细胞衰老的分子机制，希望可以进一步探索宫颈癌细胞衰老的机理，为诱导宫颈癌细胞衰老以实现宫颈癌的基因治疗寻找新的靶点。

中文关键词： 宫颈癌；细胞衰老；NEDD9

英文摘要： Inducing cellular senescence is a very promising approach to treatment of cancer. However, th mechanism of cancer cellular senescence has not yet understand. In our preliminary work, we found NEDD9 (Neural Precursor Cell Expressed, Developmentally Downregulated 9) maybe involved in the escape of cervical cancer cell from cellular senescence by using DNA microarray and western blot. In the further research, we plan to study the relationship of NEDD9 and cervical cancer cellular senescence in clinically histologic, cellular, subcellular and molecular levels by using co-immunoprecipitation, RNA interference, laser scanning confocal fluorescence microscope, flow cytometry and senescence-associated βalactosidase staining. The purposes of this project are to clear if the expression, tyrosine phosphorylation and subcellular localization of NEDD9 affect cervical cancer cellular senescence, to discuss the interaction of NEDD9 and senescence-associated proteins, and thereby to confirm the inhibition of cervical cancer cellular senescence by NEDD9, to find out the molecular mechanism how NEDD9 regulates cervical cancer cellular senescence. We hope that we can explore the mechanism of cervical cancer cellular senescence and further find out the new targets to gene therapy of cervical cancer via inducing cervical cancer cellular senescence.

英文关键词： Cervical Cancer; Cellular Senescence; NEDD9