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

A型流感病毒感染FDC-P2、BaF3和32Dc123细胞的分析 表达禽类的药物选择性逆转录病毒载体(ME26neo) 白血病病毒E26衍生的gag-myb-ets融合癌基因证实 耐药感染细胞获得继续生长的能力 促红细胞生成素(EPO)替代IL-3，增加RNA表达 针对红系转录因子GATA-1的 促红细胞生成素受体(EPOR)和β-珠蛋白需要接触EPO 至少48小时(GATA-1和EPOR)和3-5天(β-珠蛋白)。 融合癌基因的表达阻断FDC-P2细胞的凋亡 从IL-3转移到EPO，而对照组和媒介感染的细胞显示 在转换为EPO后6小时内显著凋亡，并且100% 在48小时内不可行。相比之下，ME26neo感染的FDC-P1细胞 不依赖于因子，并在转变后开始表达IL-3 无因素化媒体。不依赖因子的ME26neo感染的FDC-P1细胞 是在裸鼠体内致癌的，肿瘤的特征是 早幼粒细胞或早幼粒细胞。 对几种人类细胞系的分析表明，HEL和K562细胞 显示ETS1表达增加，但不表达ETS2、ERG-B/FLI-1或PEA3 当它们被诱导沿着红系途径分化时。 感染ETS1逆转录病毒表达载体的细胞表达 显著增加红系标志物的表达，如 血红蛋白和血糖蛋白A，并表现出对 红系特异性诱导剂，如阿糖胞苷，但不是 单核/巨噬细胞诱导性佛波酯，12-0-十四碳酰佛波酯- 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.