转录因子Pax5可不依赖与启动子结合促进B细胞淋巴瘤生长

发布时间：2018-06-09 06:30

本文选题：B细胞淋巴瘤 + Pax　；参考：《中国实验血液学杂志》2017年06期

【摘要】：目的:研究B淋巴细胞转录因子Pax5是否可以经过不依赖与启动子直接结合方式控制B细胞淋巴瘤的生长。方法:将可以产生各种突变型pax5并带GFP荧光的逆转录病毒感染小鼠淋巴瘤细胞系myc3和38B9,48 h后应用流式细胞术检测GFP+淋巴瘤细胞的比例,然后将GFP+和GFP-淋巴瘤细胞一起继续培养或皮下移植至小鼠体内生长,体外每隔3 d或体内成瘤后重新检测GFP+细胞比例并确定其细胞周期参数和凋亡细胞的数量。结果:与正常对照组(migR-GFP,空载体)相比,突变型Pax5 mt 1-357及缺乏DNA结合功能的突变型Pax5 mt 304-358和野生型Pax5一样均能明显增加GFP+细胞比例(P0.01),且S及G2/M期GFP+肿瘤细胞明显增多(P0.01),但只有DNA结合功能的Pax5 mt 1-143与空载体对照一样无法使GFP+细胞比例增加(P0.05),细胞周期也无明显改变(P0.05)。结论:Pax5可以经过不依赖与起动子直接结合方式促进B细胞淋巴瘤在体内体外的生长,其主要功能是加速肿瘤细胞分裂而不是降低细胞凋亡。本研究为以Pax5蛋白特定区域作为治疗B细胞淋巴瘤新靶点提供了理论依据。
[Abstract]:Aim: to investigate whether B lymphocyte transcription factor Pax5 can control the growth of B cell lymphoma through direct promoter independent binding. Methods: the proportion of murine lymphoma cell lines myc3 and 38B9N was detected by flow cytometry after 48 hours of retrovirus infection, which could produce various mutational types of pax5 and carry GFP fluorescence. Then GFP and GFP- lymphoma cells were cultured or subcutaneously transplanted into mice to grow in vivo. The proportion of GFP cells was determined and the cell cycle parameters and the number of apoptotic cells were determined. Results: compared with the normal control group, migR-GFP, empty carrier, The mutant Pax5mt1-357 and the mutant Pax5mt304-358, which lacks DNA binding function, can significantly increase the proportion of GFP cells (P0.01T), and S and G2 / M phase GFP tumor cells significantly increase P0.01T, but only DNA-binding Pax5mt1-143 and no-load Pax5mt1-143 can increase the proportion of GFP cells. The ratio of GFP cells to GFP cells could not be increased by P0.05, and the cell cycle did not change P0.05. Conclusion the growth of B cell lymphoma in vivo and in vitro can be promoted by the way of direct binding between cell and promoter, and its main function is to accelerate the division of tumor cells rather than to reduce apoptosis. This study provides a theoretical basis for using the specific region of Pax5 protein as a new target for the treatment of B cell lymphoma.
【作者单位】：苏州大学附属第一医院;江苏省血液研究所;苏州大学造血干细胞移植研究所;卫生部血栓与止血重点实验室;苏州大学血液学协同创新中心;扬州大学-江苏省非编码RNA基础与临床转化重点实验室;
【基金】：国家自然科学基金面上项目(81670186-郁);国家自然科学基金面上项目(81270617、81470346-吴) 江苏省高层次创新创业人才计划-重点科技创新项目(郁) 江苏省科教兴卫工程-临床医学中心(ZX201102-吴) 江苏省自然科学基金项目(BK20130454-张) 江苏省血液病临床医学研究中心(江苏省科技厅生命健康专项-BL2012005-吴) 国家临床重点专科建设项目江苏省创新能力建设专项(BM2015004-吴)
【分类号】：R733.1

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