Patel G, Kreider B, Rovera G, Reddy E P
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Mol Cell Biol. 1993 Apr;13(4):2269-76. doi: 10.1128/mcb.13.4.2269-2276.1993.
To understand the effects of v-myb expression on mammalian hematopoietic cell differentiation, we have constructed a retroviral vector which can efficiently express v-myb gene product in mammalian cells. Infection of interleukin-3-dependent murine progenitor cell line 32D Cl3, which undergoes terminal differentiation to mature granulocytes in the presence of granulocyte colony-stimulating factor (GCSF), with this recombinant retrovirus does not abrogate its requirement of interleukin-3 for growth. However, expression of v-myb in these cells blocks their ability to differentiate in response to GCSF. Instead, the v-myb-infected cells proliferate indefinitely in the presence of GCSF. 32D Cl3 cells infected with empty vector carrying only the neomycin resistance gene responded to the addition of GCSF in a manner identical to that of the uninfected cells and underwent terminal differentiation into granulocytes. These results suggest that oncogenic forms of myb gene bring about transformation by blocking the differentiation signal derived by cytokines while promoting the proliferative signal transduction pathways.
为了解v-myb表达对哺乳动物造血细胞分化的影响，我们构建了一种逆转录病毒载体，该载体可在哺乳动物细胞中高效表达v-myb基因产物。用这种重组逆转录病毒感染白细胞介素-3依赖的小鼠祖细胞系32D Cl3（该细胞系在粒细胞集落刺激因子（GCSF）存在下会终末分化为成熟粒细胞），并未消除其生长对白细胞介素-3的需求。然而，这些细胞中v-myb的表达阻断了它们对GCSF作出反应而分化的能力。相反，被v-myb感染的细胞在GCSF存在下无限增殖。用仅携带新霉素抗性基因的空载体感染的32D Cl3细胞，对添加GCSF的反应方式与未感染细胞相同，并终末分化为粒细胞。这些结果表明，myb基因的致癌形式通过阻断细胞因子衍生的分化信号，同时促进增殖信号转导途径来实现转化。
