Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism
Expression of bcr-abl abrogates factor-dependent growth of human hematopoietic M07E cells by an autocrine mechanism
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bcr-abl 的表达通过自分泌机制消除人造血 M07E 细胞的因子依赖性生长
DOI：
10.1182/blood.v83.6.1575.1575
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发表时间：
1994
期刊：
影响因子：
20.3
通讯作者：
J. Dick
中科院分区：
文献类型：
--
作者：
C. Sirard;P. Laneuville;J. Dick
将表达p210 bcr-abl（P210）的逆转录病毒载体导入人因子依赖性细胞系M07 E中，导致因子非依赖性细胞的快速生长。感染后早期，分离出四个因子独立的克隆，并与从单独感染获得的大量群体一起沿着进行更详细的分析。高水平的P210酪氨酸激酶活性在因子非依赖性细胞中测量。大规模的人口和四个克隆中的三个仍然对外源生长因子有反应。从非依赖因子的人群和所有克隆中分离的浓缩条件培养基含有生物活性粒细胞-巨噬细胞集落刺激因子（GM-CSF）;在大量人群和两个克隆中检测到低水平的白细胞介素-3（IL-3）。IL-3、GM-CSF和肥大细胞生长因子的中和抗体抑制了60%至90%的因子应答克隆的增殖。这些结果表明，表达P210的M07 E细胞的生长自主性是通过自分泌机制获得的。除了因子非依赖性生长外，与对照M07 E细胞相比，表达P210的M07 E细胞容易获得更成熟的巨核细胞表型。这些数据提供的实验证据表明，P210酪氨酸激酶在人造血细胞中的表达诱导生长因子分泌，导致对生长因子依赖性和分化的多效性效应。
The introduction of a retrovirus vector expressing p210bcr-abl (P210) into the human factor-dependent cell line M07E resulted in the rapid outgrowth of factor-independent cells. Early after infection, four factor-independent clones were isolated and analyzed in greater detail along with mass populations obtained from separate infections. High levels of P210 tyrosine kinase activity were measured in the factor- independent cells. The mass populations and three of the four clones remained responsive to exogenous growth factors. Concentrated conditioned media isolated from the factor-independent populations and from all clones contained biologically active granulocyte-macrophage colony-stimulating factor (GM-CSF); interleukin-3 (IL-3) was detected at low levels in the mass population and in two of the clones. Neutralizing antibodies to IL-3, GM-CSF, and mast cell growth factor inhibited proliferation of the factor responsive clones by 60% to 90%. These results indicate that the growth autonomy of the P210-expressing M07E cells was acquired via an autocrine mechanism. In addition to factor-independent growth, P210-expressing M07E cells readily acquired a more mature megakaryocytic phenotype compared with control M07E cells. These data provide experimental evidence that expression of P210 tyrosine kinase in human hematopoietic cells induced growth factor secretion resulting in a pleiotropic effect on growth factor dependence and differentiation.
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DOI：
10.1126/science.2551043
发表时间：
1989
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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影响因子：
20.3
作者：
Young,DC;Griffin,JD
通讯作者：
Griffin,JD
影响因子：
56.9
作者：
DALEY, GQ;VANETTEN, RA;BALTIMORE, D
通讯作者：
BALTIMORE, D
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DOI：
10.1073/pnas.82.10.3306
发表时间：
1985
影响因子：
11.1
作者：
Oliff,A;Agranovsky,O;McKinney,MD;Murty,VV;Bauchwitz,R
通讯作者：
Bauchwitz,R