Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis
Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis
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DOI：
10.1038/sj.leu.2400556
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发表时间：
1997-02-01
期刊：
影响因子：
11.4
通讯作者：
Gabrilove, JL
中科院分区：
文献类型：
--
作者：
Konig, A;Menzel, T;Gabrilove, JL
碱性成纤维细胞生长因子 (bFGF) 是一种多效细胞因子，最近被证明可以延迟氟达拉滨诱导的 B 细胞慢性淋巴细胞白血病 (B-CLL) 细胞凋亡。为了研究 bFGF 介导的细胞凋亡延迟的潜在机制，使用两种 EBV 转化的 B 幼淋巴细胞系（JVM-2、JVM-13）、一种 EBV 转化的 B-CLL 细胞系（I83CLL）和一种非 EBV 转化的 B-CLL 细胞系（WSU-CLL）作为慢性淋巴恶性肿瘤模型， 单独使用氟达拉滨或与 bFGF 联合处理的细胞证明，向细胞中添加 bFGF 可以延长存活时间，通过原位 TdT 标记对凋亡相关 DNA 链断裂进行定量评估，显示 bFGF 对氟达拉滨处理的细胞具有保护作用。Northern 分析了 bFGF 对 bcl-2 mRNA 表达的潜在影响 印迹法，bFGF 刺激导致所有三种细胞系中 bcl-2 特异性 mRNA 的时间依赖性积累。bcl-2 mRNA 表达的最大水平在 JVM-5 中 8 小时后出现缺陷，在 JVM-13 和 183CLL 中 18 小时后出现缺陷。还发现，在 EBV 和非 EBV 转化的细胞中，bFGF 刺激后细胞内 bcl-2 蛋白增加。此外，将三名 B CLL 患者的细胞暴露于 bFGF 4-8 小时后显示 bFGF 上调。我们的数据表明，bFGF 上调这些细胞中 bcl-2 的表达，表明 bFGF 表达的这种增加可能在延迟 氟达拉滨诱导细胞凋亡。
Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine which has recently been shown to delay fludarabine-induced apoptosis in B cell chronic lymphocytic leukemia (B-CLL) cells. To investigate the potential mechanism of bFGF-mediated delay of apoptosis, two EBV-transformed B prolymphocytic cell lines (JVM-2, JVM-13), one EBV-transformed B-CLL cell line (I83CLL), and one non-EBV-transformed B-CLL cell line (WSU-CLL) were used as a model for chronic lymphoid malignancies, Viability data of cells treated with fludarabine alone or in combination with bFGF demonstrated that the addition of bFGF to the cells resulted in prolonged survival, Quantitative assessment of apoptosis-associated DNA strand breaks by in situ TdT labeling showed a protective effect of bFGF on fludarabine-treated cells, The potential effect of bFGF on bcl-2 mRNA expression was analyzed by Northern blotting, Stimulation with bFGF led to a time-dependent accumulation of bcl-2 specific mRNA in all three cell lines, Maximal levels of bcl-2 mRNA expression were defected after 8 h in JVM-5, and after 18 h in JVM-13 and 183CLL. Intracellular bcl-2 protein was also found to be increased upon bFGF stimulation rn both EBV- and non-EBV-transformed cells, In addition, exposure of cells from three patients with B CLL to bFGF showed an upregulation of bcl-2 protein after 4-8 h, Our data demonstrate that bFGF upregulates the expression of bcl-2 in these cells, suggesting that this increase in bcl-2 expression may play a role in the delay of fludarabine-induced apoptosis.