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

一种复制缺陷型肿瘤细胞的致癌和生长改变特性 表达gag-myb-ets融合蛋白的鼠逆转录病毒构建体ME 26 禽急性白血病病毒的癌基因E26被用于 研究myb和ets在哺乳动物系统中的致癌潜力， myb和ets在正常和异常生长发育中的作用。 一 已经开发了这种病毒的药物选择版本（MA 26），它 已经表明，与其ME 26同源物一样，它诱导FDC-P2细胞， 小鼠IL 3依赖性骨髓来源的细胞系，在 红细胞激素促红细胞生成素（epo）代替IL 3。 的相对 药物选择的MA 26感染细胞库中FDC-P2细胞的数量是 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子是必要的， 在培养的FDC-P2细胞中的epo反应性。 用MA 26诱导 在其它鼠IL 3依赖性细胞系中的epo依赖性生长。 只有那些 表达可检测水平的红细胞特异性 转录因子加塔-1能够在MA 26后在epo中生长 感染 这表明，MA 26不能诱导重组质粒的从头表达。 加塔-1和epoR，并提示gag-myb-ets诱导的靶点。 红白血病可以是红系定型的、表达加塔-1的细胞。 它 还观察到FDC-P1细胞，一种早幼粒细胞IL 3依赖性鼠 细胞系，在MA 26或ME 26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，因为一种敏感因子 抗IL-3抗体的抗体通过MA 26释放到培养液中。 感染的非因子依赖性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 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.