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首页> 外文期刊>Molecular and Cellular Biology >A constitutively activated erythropoietin receptor stimulates proliferation and contributes to transformation of multipotent, committed nonerythroid and erythroid progenitor cells.
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A constitutively activated erythropoietin receptor stimulates proliferation and contributes to transformation of multipotent, committed nonerythroid and erythroid progenitor cells.

机译：组成型激活的促红细胞生成素受体刺激增殖，并有助于转化多能，定型的非红系和红系祖细胞。

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If the env gene of spleen focus-forming virus (SFFV) is replaced by a cDNA encoding a constitutively active form of the erythropoietin receptor, EPO-R(R129C), the resultant recombinant virus, SFFVcEPO-R, induces transient thrombocytosis and erythrocytosis in infected mice. Clonogenic progenitor cell assays of cells from the bone marrow and spleens of these infected mice suggest that EPO-R(R129C) can stimulate proliferation of committed megakaryocytic and erythroid progenitors as well as nonerythroid multipotent progenitors. From the spleens of SFFVcEPO-R-infected mice, eight multiphenotypic immortal cell lines were isolated and characterized. These included primitive erythroid, lymphoid, and monocytic cells. Some expressed proteins characteristic of more than one lineage. All cell lines resulting from SFFVcEPO-R infection contained a mutant form of the p53 gene. However, in contrast to infection by SFFV, activation of PU.1 gene expression, by retroviral integration, was not observed. One cell line had integrated a provirus upstream of the fli-1 gene, in a location typically seen in erythroleukemic cells generated by Friend murine leukemia virus infection. This event led to increased expression of fli-1 in this cell line. Thus, infection by SFFVcEPO-R can induce proliferation and lead to transformation of nonerythroid as well as very immature erythroid progenitor cells. The sites of proviral integration in clonal cell lines are distinct from those in SFFV-derived lines.
机译：如果将脾脏聚焦形成病毒（SFFV）的env基因替换为编码促红细胞生成素受体EPO-R（R129C）的组成型活性形式的cDNA，则所得重组病毒SFFVcEPO-R会在体内诱导短暂的血小板增多和红细胞增多被感染的小鼠。对这些感染小鼠的骨髓和脾脏细胞进行的克隆性祖细胞分析表明，EPO-R（R129C）可以刺激定型的巨核和红系祖细胞以及非红系多能祖细胞的增殖。从感染SFFVcEPO-R的小鼠的脾脏中分离并鉴定了八种多表型永生细胞系。这些包括原始红系，淋巴样和单核细胞。一些表达的蛋白质具有不止一种谱系的特征。由SFFVcEPO-R感染产生的所有细胞系均含有p53基因的突变形式。但是，与SFFV感染相反，未观察到逆转录病毒整合激活PU.1基因表达。一个细胞系已整合了fli-1基因上游的原病毒，该病毒通常位于Friend鼠白血病病毒感染产生的红白血病细胞中。该事件导致该细胞系中fli-1的表达增加。因此，由SFFVcEPO-R感染可诱导增殖并导致非红系以及非常不成熟的红系祖细胞转化。克隆细胞系中原病毒整合的位点不同于SFFV衍生系中的位点。

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