Differential expression of cancer-related genes by single and permanent exposure to bone morphogenetic protein 2
Differential expression of cancer-related genes by single and permanent exposure to bone morphogenetic protein 2
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DOI：
10.1007/s00432-008-0396-0
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发表时间：
2008-11-01
影响因子：
3.6
通讯作者：
Clement, Joachim H.
中科院分区：
文献类型：
--
作者：
Steinert, Susanne;Kroll, Torsten C.;Clement, Joachim H.
目的骨形态发生蛋白（BMPs）是多种细胞功能的多功能调节因子. BMP信号网络在胚胎发生和肿瘤发生中起着关键作用。BMP（例如BMP-2）以时间和浓度依赖性方式发挥其生物学功能，但也受细胞微环境的背景调节。本研究比较了稳定高浓度BMP-2与单独应用BMP-2对乳腺癌细胞MCF-7的作用。方法采用基因芯片技术分析不同孵育方式对MCF-7细胞的影响。通过实时PCR验证数据。结果BMP-2持续高水平与单独应用BMP-2后，其基因表达的改变有明显差异。在将感兴趣的基因分组到基因本体论的生物过程中之后，在BMP-2的单次应用方案下，骨质疏松相关基因如BAX、BAG 5或PKR的组主要受到影响。在这些蛋白激酶R是最显着的调节。进一步的蛋白质水平的研究表明，激活PKR后4小时，随后增强磷酸化的PKR底物eIF 2 α的几个hours.Conclusion治疗的持续时间和BMP-2的浓度影响MCF-7细胞的全球表达模式。在受调控的癌症相关基因中，前列腺增生相关基因组显示出明显的改变。我们的数据指出BMP-2在肿瘤发生中PKR通路的调节中的新作用。
Purpose Bone morphogenetic proteins (BMPs) are multifunctional regulators of various cell functions. The BMP-signalling network plays a pivotal role during embryogenesis and tumorigenesis. BMPs, e.g. BMP-2 exert their biological function in a time and concentration-dependent manner but also modulated by the context of the cellular microenvironment. In this study, we investigated the effect of a steady high level of BMP-2 versus a single application of BMP-2 on the breast cancer cell line MCF-7.Methods The effect of the incubation regimes was analysed by DNA microarray expression profiling. Data were verified by real-time PCR. The protein expression of apoptosis-related genes was studied by western blot analysis.Results We found a clear difference in the altered gene expression between the constant high level and the single application of BMP-2. After grouping the genes of interest into the biological processes of Gene Ontology, the group of apoptosis-related genes like BAX, BAG5 or PKR, was predominantly affected under the single-application regime of BMP-2. Among these protein kinase R was the most prominently regulated. Further studies on the protein level showed activation of PKR after 4 h with a subsequent enhanced phosphorylation of the PKR substrate eIF2alpha for several hours.Conclusion The duration of treatment and the concentration of BMP-2 affect the global expression pattern of MCF-7 cells. Among the regulated cancer-related genes, the cohort of the apoptosis-related genes showed the pronounced alterations. Our data point to a novel role of BMP-2 in the regulation of the PKR pathway in tumorigenesis.