Inhibition of proliferation and differentiation and promotion of apoptosis by cyclin L2 in mouse embryonic carcinoma P19 cells.
Inhibition of proliferation and differentiation and promotion of apoptosis by cyclin L2 in mouse embryonic carcinoma P19 cells.
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DOI：
10.1016/j.bbrc.2009.09.089
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发表时间：
2009-12
影响因子：
3.1
通讯作者：
L. Zhuo;J. Gong;Rong Yang;Yan-hui Sheng;Lei Zhou;X. Kong;K. Cao
中科院分区：
文献类型：
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作者：
L. Zhuo;J. Gong;Rong Yang;Yan-hui Sheng;Lei Zhou;X. Kong;K. Cao
细胞周期蛋白L2（CCNL 2）是细胞周期蛋白基因家族的新成员。在先前的研究中，我们证明了与健康对照相比，室间隔缺损患者的室间隔组织中CCNL 2表达上调。在本研究中，我们建立了一个稳定的CCNL 2过表达P19细胞系，可以分化为心肌细胞时，用1%的二甲基亚砜（DMSO）。我们的数据显示，稳定的CCNL 2过表达的P19细胞在用1%DMSO处理后分化程度较低，并且与仅转染载体的P19相比，心肌细胞分化相关基因（如心脏肌动蛋白、GATA 4、Mef 2C、Nkx 2.5和BNP）的表达降低。此外，过表达CCNL 2基因的P19细胞具有降低的生长速率和显著减少的S期。我们还发现，这些细胞发生凋亡，检测两种不同的凋亡测定。抗凋亡Bcl-2蛋白在这些细胞中也下调。实时荧光定量PCR分析显示，CCNL 2过表达的P19细胞中Wnt和β-catenin的表达受到抑制，GSK 3 β的表达受到诱导。这些数据表明，CCNL 2的过表达抑制了小鼠胚胎癌P19细胞的增殖和分化，并诱导它们发生细胞凋亡，这可能是通过Wnt信号传导途径实现的。
Cyclin L2 (CCNL2) is a novel member of the cyclin gene family. In a previous study, we demonstrated that CCNL2 expression was upregulated in ventricular septum tissues from patients with ventricular septal defect compared to healthy controls. In the present study, we established a stable CCNL2-overexpressing P19 cell line that can differentiate to myocardial cells when treated with 1% dimethyl sulfoxide (DMSO). Our data showed that stable CCNL2-overexpressing P19 cells were less differentiated after treatment with 1% DMSO and that expression of myocardial cell differentiation-related genes (such as cardiac actin, GATA4, Mef2C, Nkx2.5, and BNP) were reduced compared to vector-only transfected P19. Moreover, P19 cells overexpressing the CCNL2 gene had a reduced growth rate and a remarkably decreased S phase. We also found that these cells underwent apoptosis, as detected by two different apoptosis assays. The anti-apoptotic Bcl-2 protein was also downregulated in these cells. In addition, real-time PCR analysis revealed that expression of Wnt and β-catenin was suppressed and GSK3β was induced in the CCNL2-overexpressing P19 cells. These data suggest that overexpression of CCNL2 inhibited proliferation and differentiation of mouse embryonic carcinoma P19 cells and induced them to undergo apoptosis, possibly through the Wnt signal transduction pathway.