Oncogene cooperativity in Friend erythroleukemia: erythropoietin receptor activation by the env gene of SFFV leads to transcriptional upregulation of PU.1, independent of SFFV proviral insertion
Oncogene cooperativity in Friend erythroleukemia: erythropoietin receptor activation by the env gene of SFFV leads to transcriptional upregulation of PU.1, independent of SFFV proviral insertion
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DOI：
10.1038/sj.onc.1205183
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发表时间：
2002-02-14
期刊：
影响因子：
8
通讯作者：
Longmore, GD
中科院分区：
文献类型：
--
作者：
Afrikanova, I;Yeh, E;Longmore, GD
癌症是一个多步骤、多基因事件。致癌突变是否相互合作转化细胞以及如何转化尚不清楚。Friend鼠逆转录病毒红白血病模型涉及病毒env基因（F-gp 55）对促红细胞生成素受体（EpoR）的促有丝分裂激活、转录因子PU.1的异常过表达和p53的失活突变。在这份报告中，我们证明了在红系靶细胞中同时表达F-gp 55和PU.1，在体内，合作加速红白血病诱导。在疾病早期，在检测到克隆性白血病细胞之前，F-gp 55激活EpoR，而不是促红细胞生成素，通过反式调节机制导致PU.1的转录上调。这可能发生在PU.1基因座内没有整合的前病毒的情况下。在已建立的红白血病细胞系中，PU.1转录的调节取决于PU.1蛋白存在的水平。我们的研究结果表明，F-gp 55的行动有助于早期和晚期的朋友红白血病和持久的F-gp 55表达可能不仅需要启动红白血病，但也维持红白血病后朋友病毒感染。
Cancer is a multi-step, multi-genetic event. Whether oncogenic mutations cooperate with one another to transform cells and how is not well understood. The Friend murine retroviral erythroleukemia model involves mitogenic activation of the erythropoietin receptor (EpoR) by the virus env gene (F-gp55), aberrant over-expression of the transcription factor PU.1, and inactivating mutations in p53. In this report we demonstrate that concurrent expression of F-gp55 and PU.1 in erythroid target cells, in vivo, cooperate to accelerate erythroleukemia induction. Early in the disease, prior to the detection of clonal leukemic cells, activation of the EpoR by F-gp55, but not erythropoietin, resulted in transcriptional upregulation of PU.1 through a trans regulatory mechanism. This could occur in the absence of an integrated provirus within the PU.1 gene locus. The regulation of PU.1 transcription in established erythroleukemia cell lines differed depending upon the level of PU.1 protein present. Our results suggest that the action of F-gp55 contributes to both early and late stages of Friend erythroleukemia and that persistence of F-gp55 expression may be required not only to initiate erythroleukemia but to also maintain erythroleukemia following Friend virus infection.