PSF易位细胞膜负调控血液肿瘤多药耐药的作用与分子机制

项目名称： PSF易位细胞膜负调控血液肿瘤多药耐药的作用与分子机制

项目编号： No.81201729

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 任思楣

作者单位： 卫生部北京医院

项目金额： 23万元

中文摘要： 肿瘤多药耐药是涉及细胞内多种基因和蛋白改变、多种机制参与的复杂生物学过程。申请人在白血病耐药相关膜蛋白抗体的研究中通过一株单抗在国内外首次证实细胞核蛋白PSF可易位表达于血液肿瘤细胞表面，且在敏感HL60细胞膜上表达高于耐药HL60/ADR细胞，经该抗体处理后，HL60细胞对阿霉素敏感性和增殖能力显著改变，推测膜易位PSF可能为一新的负调控血液肿瘤多药耐药蛋白。本研究将构建细胞膜蛋白易位表达载体，使PSF在血液肿瘤细胞膜高表达，进一步研究PSF易位细胞膜情况下介导的血液肿瘤耐药及其耐药谱；在耐药动物模型和临床样本中验证PSF膜易位介导的耐药；研究PSF易位细胞膜的分子机制及通过调控血液肿瘤细胞增殖相关生物学特性负调控肿瘤耐药的分子机制。该研究将深入揭示由易位膜蛋白介导的血液肿瘤多药耐药的分子机制，为设计合理的耐药逆转剂和多药耐药预测靶点提供实验基础。

中文关键词： 白血病；多药耐药；PSF；蛋白质易位；

英文摘要： Accumulating evidence suggests that a variety of changes on genes and proteins and multiple complex mechanisms maybe involved, in the emergence and development of multidrug resistance (MDR) in various cancers. During a study on monoclonal antibodies reacted with MDR associated membrane proteins, we first confirmed relocation of nucleoprotein PSF on cell surface in neoplastic hematologic disorder, and PSF overexpression on HL60 cell surface compared to its MDR HL60/ADR cells. We also observed that the sensitivity and proliferation were improved significantly by antibody treatment. Our results suggest that relocated membrane PSF may be a new negative regulator of MDR protein in hematologic neoplasa. In this study, we will reconstruct PSF expression on the non-expression of haematological tumor cell lines, and further investigate MDR mediated by relocated membrane PSF including the MDR mechanisms and drug spectrum, MDR in animal models and patients. We will also study the molecular mechanisms of the PSF relocation to the cell membrane. The investigations cloud further reveal the MDR molecular mechanism mediated by relocated membrane PSF, which will provide the experimental evidence for befitting targets of reversal agents and MDR clinical prediction.

英文关键词： leukemia；multidrug resistance；PSF；protein relocation；