Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity.
Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity.
复制标题
PP2Calpha在细胞生长，放射性和化学敏感性以及致瘤性中的作用。
DOI：
10.1186/1476-4598-6-65
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发表时间：
2007-10-17
期刊：
影响因子：
37.3
通讯作者：
Huber, Peter
中科院分区：
文献类型：
--
作者：
Lammers, Twan;Peschke, Peter;Ehemann, Volker;Debus, Jurgen;Slobodin, Boris;Lavi, Sara;Huber, Peter
PP2Cα是2C型蛋白磷酸酶家族的代表成员，它最近被认为与p53-、tgf -、细胞周期蛋白依赖性激酶-和凋亡信号的调控有关。为了研究PP2Cα在细胞生长和放化疗敏感性中的作用，我们对野生型和表达PP2Cα sirna的MCF7细胞在基础条件和放化疗条件下进行了几种不同的活力和细胞周期分析。通过比较两种细胞的肿瘤生长情况，我们还评估了PP2Cα在肿瘤发生中的作用。结果表明，敲低PP2Cα不影响MCF7细胞的增殖、克隆存活和膜完整性。此外，它并没有改变他们的放射和化学敏感性。对于表达PP2Cα sirna的MCF7细胞，处于细胞周期G0/G1期的细胞数量减少，G1阻断的诱导作用减弱，处于G2/M期的细胞数量增加，G2阻断的诱导作用增强。结果发现，表达PP2Cα sirna的MCF7细胞的致瘤潜能高于野生型MCF7细胞，且MCF7细胞的体内增殖能力增强。基于这些发现，我们得出结论，PP2Cα在体外不参与控制细胞生长和放射和化学敏感性。然而，它确实在细胞周期的调节、细胞周期检查点的诱导和肿瘤发生中发挥作用。后一种观点暗示PP2Cα可能具有肿瘤抑制特性，从而为更详细地分析其在癌症发生和进展中的作用奠定了基础。
PP2Cα is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFβ-, cyclin-dependent kinase- and apoptosis-signaling. To investigate the role of PP2Cα in cell growth and in radio- and chemosensitivity, wild type and PP2Cα siRNA-expressing MCF7 cells were subjected to several different viability and cell cycle analyses, both under basal conditions and upon treatment with radio- and chemotherapy. By comparing the growth of tumors established from both types of cells, we also evaluated the involvement of PP2Cα in tumorigenesis. It was found that knockdown of PP2Cα did not affect the proliferation, the clonogenic survival and the membrane integrity of MCF7 cells. In addition, it did not alter their radio- and chemosensitivity. For PP2Cα siRNA-expressing MCF7 cells, the number of cells in the G0/G1 phase of the cell cycle was reduced, the induction of the G1 block was attenuated, the number of cells in G2/M was increased, and the induction of the G2 block was enhanced. The tumorigenic potential of PP2Cα siRNA-expressing MCF7 cells was found to be higher than that of wild type MCF7 cells, and the in vivo proliferation of these cells was found to be increased. Based on these findings, we conclude that PP2Cα is not involved in controlling cell growth and radio- and chemosensitivity in vitro. It does, however, play a role in the regulation of the cell cycle, in the induction of cell cycle checkpoints and in tumorigenesis. The latter notion implies that PP2Cα may possess tumor-suppressing properties, and it thereby sets the stage for more elaborate analyses on its involvement in the development and progression of cancer.