STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells
STAT5 activation contributes to growth and viability in Bcr/Abl-transformed cells
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DOI：
10.1182/blood.v95.6.2118
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发表时间：
2000-03-15
期刊：
影响因子：
20.3
通讯作者：
Griffin, JD
中科院分区：
文献类型：
--
作者：
Sillaber, C;Gesbert, F;Griffin, JD
转录因子STAT 5在造血细胞被p210 Bcr/Abl转化后被组成型酪氨酸磷酸化和激活。将缺失酪氨酸699和转录激活结构域的STAT 5 B的截短形式（Delta STAT 5; as，1-683）引入到四环素诱导型启动子控制下的Ba/F3 p210细胞中。用四环素类似物强力霉素处理这些细胞，诱导Delta STAT 5的表达并抑制STAT 5依赖性转录。Delta STAT 5与STAT 5共沉淀，并降低内源性STAT 5的Bcr/Bcr依赖性酪氨酸磷酸化。Delta STAT 5的诱导抑制Ba/F3 p210细胞的生长（在4天时为对照水平的26%-52%），但不引起细胞周期停滞。Delta STAT 5降低Ba/F3 p210细胞的存活力并增加细胞对细胞毒性药物羟基脲和阿糖胞苷的敏感性。这些结果表明，如本文通过使用四环素诱导型启动子实现的Delta STAT 5的高水平表达抑制STAT 5活性，通过抑制存活力降低Ba/F3 p210细胞的生长速率，并导致对化疗药物的敏感性增加。因此，STAT 5激活可能在p210 Bcr/Bcr对造血细胞系的转化中起作用。（C）2000，美国血液学会。
The transcription factor STAT5 is constitutively tyrosine phosphorylated and activated after transformation of hematopoietic cells by p210Bcr/Abl, A truncated form of STAT5B (Delta STAT5; as, 1-683) that lacks tyrosine 699 and the transcriptional activation domain was introduced into Ba/F3p210 cells under the control of a tetracycline-inducible promoter. Treatment of these cells with doxycycline, a tetracycline analogue, induced expression of Delta STAT5 and inhibited STAT5-dependent transcription. Delta STAT5 coprecipitated with STAT5 and decreased Bcr/Abl-dependent tyrosine phosphorylation of endogenous STAT5. Induction of Delta STAT5 inhibited growth of Ba/F3p210 cells (26%-52% of control levels at 4 days) but did not cause cell-cycle arrest. Delta STAT5 reduced viability of Ba/F3p210 cells and increased sensitivity of the cells to the cytotoxic drugs hydroxyurea and cytarabine, These results indicate that high-level expression of Delta STAT5, as achieved here by using a tetracycline-inducible promoter, inhibits STAT5 activity, reduces the growth rate of Ba/F3p210 cells by inhibiting viability, and results in increased sensitivity to chemotherapeutic drugs, It Is therefore likely that STAT5 activation plays a role in the transformation of hematopoietic cell lines by p210Bcr/Abl. (C) 2000 by The American Society of Hematology.