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

复制缺陷的致癌和生长改变特性 表达Gag-myb-ETS融合基因的小鼠逆转录病毒载体ME26 禽类急性白血病病毒E26的致癌基因正被用于 研究MYB和ETS在哺乳动物系统中的致癌潜力，以及 MYB和ETS在正常和异常生长发育中的作用一个 这种病毒的药物选择版本(MA26)已经开发出来，它 已经证明，像它的ME26同源物一样，它诱导FDC-P2细胞，一个 小鼠白细胞介素3依赖的骨髓源性细胞系在 红系激素促红细胞生成素(EPO)替代IL3。相对的 药物选择的MA26感染细胞池中的FDC-P2细胞数量为 低，尽管表达了高水平的病毒信息。这些 结果表明额外的细胞和病毒因素是诱导 体外培养的FDC-P2细胞对EPO的反应性。用MA26诱导 其他小鼠IL-3依赖细胞系中EPO依赖的生长。只有那些 表达可检测到的红系特异性水平的细胞 转录因子GATA-1能够在MA26后的EPO中生长 感染。这表明MA26不能诱导原核表达。 GATA-1和EPOR，提示了GAG-MYB-ETS诱导的靶点 红白血病可能是一种红系依赖的、表达GATA-1的细胞。它 还观察到FDC-P1细胞，一种依赖IL-3的早幼粒细胞 细胞株，在MA26或ME26感染后变得不依赖于因子。 这似乎是通过自分泌机制发生的，因为一个敏感的因素 通过MA26将抗IL3抗体释放到培养液中- 感染的非因子依赖的FDC-P1细胞。这些结果表明，在 在适当的细胞背景下，gag-myb-ets融合癌基因可以 影响IL-3的表达。

The oncogenic and growth-altering properties of a replication-defective murine retrovirus construct, ME26, which expresses the gag-myb-ets fusion oncogene of the avian acute leukemia virus, E26, is being utilized to study the oncogenic potential of myb and ets in mammalian systems, and the role of myb and ets in normal and abnormal growth and development. A drug-selectable version of this virus (MA26) has been developed, and it has been shown that, like its ME26 homolog, it induces FDC-P2 cells, a murine IL3-dependent, bone marrow-derived cell line, to grow in the erythroid hormone erythropoietin (epo) in place of IL3. The relative number of FDC-P2 cells in a drug-selected pool of MA26-infected cells is low, despite the expression of high levels of viral message. These results suggest additional cell and viral factors are necessary to induce epo responsiveness in FDC-P2 cells in culture. MA26 was used to induce epo-dependent growth in other murine IL3-dependent cell lines. Only those cells which express detectable levels of the erythroid-specific transcription factor GATA-1 are able to grow in epo following MA26 infection. This indicates that MA26 cannot induce de novo expression of GATA-1 and the epoR, and suggests the target of gag-myb-ets-induced erythroleukemia may be an erythroid-committed, GATA-1-expressing cell. It was also observed that FDC-P1 cells, a promyelocytic IL3-dependent murine cell line, becomes factor-independent following MA26 or ME26 infection. This appears to occur by an autocrine mechanism, since a factor sensitive to anti-IL3 antibodies is released into the culture fluid by MA26- infected, factor-independent FDC-P1 cells. These results suggest that in the appropriate cell background, the gag-myb-ets fusion oncogene can affect the expression of IL3.