Athanasiou M, Mavrothalassitis G J, Yuan C C, Blair D G
Laboratory of Cellular Biochemistry, SAIC Frederick, Maryland, USA.
Oncogene. 1996 Jan 18;12(2):337-44.
Expression of the avian E26-derived Gag-Myb-Ets fusion oncogene in interleukin-3(IL3)-dependent murine hematopoietic cell lines results in a pattern of cell line dependent changes in growth factor-induced proliferation and apoptosis. A drug-selectable retrovirus expressing p135Gag-Myb-Ets induced an erythropoietin(Epo)-responsive phenotype in the cell lines FDC-P2, BaF3 and 32Dc123. Gag-Myb-Ets expression alone did not increase expression of GATA-1 or the Epo receptor(EpoR) in the presence of IL3, and infected cell lines express increased GATA-1 and EpoR only when IL3 was replaced by Epo in the culture media. Indicative of Epo-induced erythroid differentiation, these cells also began to express beta-globin after 3-5 days growth in Epo. Unlike control cells, infected FDC-P2 cells failed to undergo programmed cell death (apoptosis) when transferred from IL3- to Epo-containing media, although a fraction of the cells failed to proliferate following the media shift. Three other IL3-dependent cell lines showed no changes in growth behavior when induced to express the fusion oncogene. Our data shows that Gag-Myb-Ets can have different affects on growth factor pathways depending on the cell background, suggesting a model in which the p135gag-myb-ets fusion oncogene promotes these different responses through its affect on apoptosis.
禽源E26衍生的Gag-Myb-Ets融合癌基因在白细胞介素-3（IL3）依赖的小鼠造血细胞系中的表达导致生长因子诱导的增殖和凋亡出现细胞系依赖性变化模式。一种表达p135Gag-Myb-Ets的药物可选择逆转录病毒在细胞系FDC-P2、BaF3和32Dc123中诱导出促红细胞生成素（Epo）反应性表型。单独的Gag-Myb-Ets表达在存在IL3的情况下不会增加GATA-1或促红细胞生成素受体（EpoR）的表达，并且只有当培养基中的IL3被Epo替代时，被感染的细胞系才会表达增加的GATA-1和EpoR。这些细胞在Epo中生长3至5天后开始表达β-珠蛋白，这表明Epo诱导了红系分化。与对照细胞不同，被感染的FDC-P2细胞从含IL3的培养基转移到含Epo的培养基时未能发生程序性细胞死亡（凋亡），尽管一部分细胞在培养基更换后未能增殖。另外三个IL3依赖的细胞系在被诱导表达融合癌基因时生长行为没有变化。我们的数据表明，Gag-Myb-Ets根据细胞背景对生长因子途径可能有不同影响，这提示了一种模型，即p135gag-myb-ets融合癌基因通过其对凋亡的影响促进这些不同反应。
