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Unregulated expression of the erythropoietin receptor gene caused by insertion of spleen focus-forming virus long terminal repeat in a murine erythroleukemia cell line.

机译:在小鼠红白血病细胞系中插入脾脏形成病毒的长末端重复序列引起的促红细胞生成素受体基因表达异常。

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A murine erythroleukemia (MEL) cell line, F5-5, expressed 10,000 binding sites for erythropoietin (EPO) per cell, 10-fold more than was expressed by other murine erythroleukemia cell lines and normal erythroid progenitors. Northern (RNA) and Southern blot analyses revealed overexpression of mRNA for the EPO receptor (EPOR) and rearrangement of one of the EPOR gene alleles in F5-5 cells, respectively. Molecular cloning of F5-5-derived cDNA encoding EPOR revealed that the 5' noncoding region of the EPOR cDNA corresponds to the 3' long terminal repeat sequence of the polycythemic strain of Friend spleen focus-forming virus (F-SFFVP). The aberrant EPOR transcripts containing the 3' long terminal repeat sequence were mainly expressed in F5-5 cells. The same integration upstream of the EPOR gene was also observed in other subclones and the parent cell line. It is possible that overexpression of EPOR by viral promoter insertion will confer growth advantage to an F-SFFVP-infected erythroid progenitor cell, leading to positive clonal selection through further leukemogenic steps.
机译:鼠类红细胞白血病(MEL)细胞系F5-5每个细胞表达10,000个促红细胞生成素(EPO)结合位点,是其他鼠类红细胞白血病细胞系和正常红系祖细胞表达的10倍。 Northern(RNA)和Southern印迹分析分别显示F5-5细胞中EPO受体(EPOR)的mRNA过表达和一个EPOR基因等位基因的重排。 F5-5衍生的编码EPOR的cDNA的分子克隆表明,EPOR cDNA的5'非编码区与Friend脾脏聚焦形成病毒(F-SFFVP)多细胞株的3'长末端重复序列相对应。包含3'长末端重复序列的异常EPOR转录物主要在F5-5细胞中表达。在其他亚克隆和亲本细胞系中也观察到了EPOR基因上游的相同整合。通过病毒启动子的插入,EPOR的过表达可能会赋予F-SFFVP感染的类红细胞祖细胞以生长优势,从而通过进一步的致白血病步骤导致克隆的阳性选择。

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