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本文报道哺乳类红细胞终末分化去核因子 (EDDF)调控恶性骨髓瘤细胞的分化以及与 EDDF相关的基因克隆的系列研究结果。以不同分化期哺乳类红细胞为研究对象 ,观察红细胞自然排核前后的细胞形态变化和与之互为对应的物质代谢的改变 ,分析 EDDF与终末分化、核浓缩及自然排核的可能关系 ;用自建的红细胞胞质体杂交模型 ,分别对红白血病和非红系的骨髓瘤细胞进行同种和异种的细胞杂交实验以验证 EDDF的作用规律。结果表明 ,哺乳类红细胞在终末分化不同阶段存在时相相关的分化去核因子家族。这些因子可调控不同分化阶段相关基因的活动 ,且呈时序性出现 ,与血红蛋白表达、细胞核停止分裂转向分化、核偏位、核浓 (固 )缩和自然去核等终末分化特征呈现明显的因果关系。 EDDF活性蛋白可逆转体外培养的肿瘤细胞系 (MEL,K5 6 2 )的恶性生长及诱导终末分化。在上述基础上分别采用不同的分离、提纯及基因克隆路线 ,从人和小鼠红细胞中连续克隆到 5种分化相关基因家族 (MEDDF,HEDDF- 1,HEDRF- 1,HEDRF- 2 ,HCNBP- 1)及其全长序列 ,并经 Gen Bank证实 ,它们均为无同源的新基因序列。
This paper reports the results of a series of studies on the differentiation of malignant myeloma cells mediated by mammalian erythrocyte terminal differentiation enucleation factor (EDDF) and gene cloning associated with EDDF. Different types of mammalian erythrocytes were used as research objects to observe changes in cell morphology before and after erythrocyte natural excretion and changes in the material metabolism that corresponded to each other. The possible relationship between EDDF and terminal differentiation, nuclear condensation, and natural excretion was analyzed. Using a self-built erythrocyte cytoplast hybridization model, erythroleukemia and non-erythroid myeloma cells were subjected to the same and different cell hybridization experiments to verify the effect of EDDF. The results showed that mammalian erythrocytes existed at different stages of terminal differentiation in a phase-related family of differentiated enucleated factors. These factors can regulate the activities of related genes at different stages of differentiation and occur in a time-sequential manner. The characteristics of terminal differentiation such as hemoglobin expression, cessation of nuclear arrest and differentiation, nuclear delocalization, nuclear condensation, and natural enucleation are obvious. Causal relationship. EDDF-active protein reverses malignant growth and induces terminal differentiation in cultured tumor cell lines (MEL, K562). On the basis of the above-mentioned separation and purification and gene cloning routes respectively, 5 different differentiation-related gene families (MEDDF, HEDDF-1, HEDRF-1, HEDRF-2, HCNBP-1) were cloned from human and mouse red blood cells. And its full-length sequence, and confirmed by Gen Bank, are all new gene sequences without homology.