Ihle J N, Askew D
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Int J Cell Cloning. 1989 Mar;7(2):68-91. doi: 10.1002/stem.5530070202.
Studies of the growth regulation, differentiation and transformation of myeloid cells have been greatly facilitated by the availability of a variety of hematopoietic growth factor-dependent cell lines. These cell lines have been isolated from long-term bone marrow cultures and myeloid tumors using interleukin 3 (IL-3) as a growth factor. Using growth factor-dependent cells, it has been shown that growth regulation by IL-3 involves binding to a high-affinity receptor of 140 Kd and activation of tyrosine phosphorylation. IL-3 binding is associated with a number of cellular responses which are required for maintenance of viability, including induction of transcription of the c-myc and ornithine decarboxylase (ODC) genes. In addition, IL-3 regulates the expression of transcription of the gamma T cell receptor locus. The properties of the IL-3-dependent lines are consistent with the hypothesis that they are transformed in their ability to terminally differentiate. In some of the cell lines, this transformation may terminally differentiate. In other of the cell lines, this transformation may be due to the altered expression of the c-myb gene. In other cell lines, transformation is associated with the activation of the expression of a novel gene, termed Evi-1, of the zinc finger family of transcriptional factors. Comparable transformation of erythroid lineage cells is speculated to be due to the activation of the expression of another novel gene termed spi-1. These studies have emphasized the value of well-characterized hematopoietic growth factor-dependent cell lines in advancing our understanding in the basic biology of myeloid cells.
多种依赖造血生长因子的细胞系的可得性极大地促进了对髓系细胞生长调节、分化和转化的研究。这些细胞系是从长期骨髓培养物和髓系肿瘤中分离出来的，使用白细胞介素3（IL-3）作为生长因子。利用依赖生长因子的细胞，已表明IL-3的生长调节涉及与140 Kd的高亲和力受体结合以及酪氨酸磷酸化的激活。IL-3结合与维持细胞活力所需的多种细胞反应相关，包括诱导c-myc和鸟氨酸脱羧酶（ODC）基因的转录。此外，IL-3调节γT细胞受体基因座转录的表达。IL-3依赖细胞系的特性与它们在终末分化能力上发生转化的假设一致。在一些细胞系中，这种转化可能导致终末分化。在其他细胞系中，这种转化可能是由于c-myb基因表达的改变。在其他细胞系中，转化与一种称为Evi-1的新型基因（转录因子锌指家族成员）表达的激活有关。推测红系谱系细胞的类似转化是由于另一种称为spi-1的新型基因表达的激活。这些研究强调了特征明确的依赖造血生长因子的细胞系在推进我们对髓系细胞基础生物学理解方面的价值。
