Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival
Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival
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DOI：
10.1038/sj.onc.1207478
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发表时间：
2004-05-06
期刊：
影响因子：
8
通讯作者：
Knudson, CM
中科院分区：
文献类型：
--
作者：
Cheng, NL;Janumyan, YM;Knudson, CM
BCL-2通过抑制细胞死亡促进肿瘤发生。在某些情况下，bcl2还可以抑制增殖和抑制肿瘤的形成。为了阐明Bcl2的抗增殖功能的作用，产生了表达突变形式的Bcl2的小鼠(酪氨酸28变为丙氨酸，Bcl2-Y28A)。不出所料，野生型(WT)和Bcl2-Y28A对细胞凋亡的抑制作用相似。与以前在细胞系中的结果相反，Bcl-2-Y28A抑制T细胞增殖的作用与WT-Bcl-2相同。值得注意的是，Bcl2-Y28A和WT-Bcl2均能抑制老年动物T细胞的增殖，但不能抑制未成熟小鼠T细胞的增殖。相反，细胞激活的抑制与T细胞大小、p27水平和RNA含量相关，这些都是静止期G0停滞的指标。与该模型一致的是，Bax的表达逆转了Bcl2对T细胞增殖的抑制，再次使细胞增殖与细胞大小相关。这些实验并不支持Bcl2对细胞凋亡和增殖的基因分离效应。相反，这些数据支持这样一种模型，即通过改变T细胞的大小和增加静止的G0停滞的标志物，Bcl2和Bax调节T细胞的增殖。这些变化可能是由于T细胞存活时间延长所致。
Bcl-2 promotes oncogenesis by inhibiting cell death. Bcl-2 also inhibits proliferation and suppresses tumorigenesis in some settings. To clarify the role of the antiproliferative function of Bcl-2, mice expressing a mutant form of Bcl-2 reported to lack antiproliferative activity were generated (tyrosine 28 to alanine, Bcl-2-Y28A). As expected, both wild type (WT) and Bcl-2-Y28A inhibited apoptosis similarly. In contrast to previous results in cell lines, Bcl-2-Y28A inhibited T-cell proliferation identical to WT-Bcl-2. Significantly, both Bcl-2-Y28A and WT-Bcl-2 inhibited proliferation of T cells isolated from older animals, but not proliferation of T cells from immature mice. Instead, inhibition of cell activation correlated with T-cell size, p27 levels, and RNA content, all indicators of quiescent G0 arrest. Consistent with this model, Bcl-2 inhibition of T-cell proliferation was reversed by expression of Bax, again correlating cell proliferation with cell size. These experiments do not support genetically separate effects of Bcl-2 on apoptosis and proliferation. Instead, the data support a model in which Bcl-2 and Bax regulate T-cell proliferation by changes in T-cell size and by increasing the markers of quiescent G0 arrest. These changes likely result from prolonged T-cell survival.