STUDIES OF E26 AVIAN V-ETS AND ITS CELLULAR HOMOLOG IN MOUSE CELLS

分析感染了一种病毒的FDC-P2、BaF 3和32 Dc 123细胞 表达禽流感病毒的药物选择性逆转录病毒构建体（ME 26 neo） 白血病病毒E26衍生的gag-myb-ets融合癌基因证实， 耐药感染细胞获得生长的能力 促红细胞生成素（EPO）替代IL-3，并增加RNA表达 特异于红系转录因子加塔-1， 促红细胞生成素受体（EpoR）和β-珠蛋白需要暴露于EPO 至少48小时（加塔-1和EpoR）和3-5天（β-珠蛋白）。 融合癌基因的表达阻断FDC-P2细胞凋亡 从IL-3转移到EPO，而对照和载体感染的细胞显示 在转换为EPO后6小时内发生显著的细胞凋亡，并且100% 48小时内不能存活 相比之下，ME 26 neo感染的FDC-P1细胞 变得不依赖于因子，并在转移后开始表达IL-3， 到无因子媒体。 因子非依赖性ME 26 neo感染的FDC-P1细胞 在裸鼠中是致瘤的，并且肿瘤的特征在于： 早期髓细胞或早幼粒细胞。 对几种人细胞系的分析表明，HEL和K562细胞 ETS 1表达增加，但ETS 2、ERG-B/FLI-1或PEA 3表达不增加 当它们被诱导沿着红细胞途径分化沿着时。 用ETS 1逆转录病毒表达构建体感染的细胞表达 显著增加的红系标志物表达，例如 血红蛋白和血型糖蛋白A，并表现出对 红细胞特异性诱导剂，如阿糖胞苷，但不是 单核细胞/巨噬细胞诱导佛波酯，12-0-十四酰基佛波酯， 13-乙酸酯

Analysis of FDC-P2, BaF3, and 32Dc123 cells infected with a drug-selectable retroviral construct (ME26neo) expressing the avian leukemia virus E26-derived gag-myb-ets fusion oncogene demonstrated that drug-resistant infected cells acquire the capacity to grow on erythropoietin (EPO) in place of IL-3, and increased expression of RNA specific for the erythroid transcription factor GATA-1, the erythropoietin receptor (EpoR) and beta-globin requires exposure to EPO for at least 48 hours (GATA-1 and EpoR) and 3-5 days (beta-globin). Expression of the fusion oncogene blocked apoptosis in FDC-P2 cells shifted from IL-3 to EPO, while control and vector-infected cells showed significant apoptosis within 6 hours of a shift to EPO and were 100% nonviable within 48 hours. In contrast, ME26neo-infected FDC-P1 cells became factor-independent, and began to express IL-3 following a shift to factor-free media. Factor-independent, ME26neo- infected FDC-P1 cells were tumorigenic in nude mice, and tumors were characterized as early-stage myelocytic or promyelocytic. Analysis of several human cell lines indicated that HEL and K562 cells showed increased expression of ETS1, but not ETS2, ERG-B/FLI-1, or PEA3 when they were induced to differentiate along an erythroid pathway. Cells infected with an ETS1 retroviral expression construct expressed significantly increased expression of erythroid markers, such as hemoglobin and glycophorin A, and exhibited an increased sensitivity to erythroid-specific inducers, such as cytosine arabinoside, but not the monocyte/macrophage-inducing phorbol ester, 12-0-tetradecauoylphorbol- 13-acetate.