P53 and beta-catenin activity during estrogen treatment of osteoblasts.
P53 and beta-catenin activity during estrogen treatment of osteoblasts.
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DOI：
10.1186/1475-2867-5-24
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发表时间：
2005-07-29
影响因子：
5.8
通讯作者：
Prozialeck WC
中科院分区：
文献类型：
--
作者：
Chandar N;Saluja R;Lamar PC;Kolman K;Prozialeck WC
本研究旨在探讨抑癌基因 p53 与核信号蛋白 β-catenin 在骨分化过程中的关系。 p53 和 β-catenin 通路之间的串扰已被证实，并且在肿瘤发生和 DNA 损伤过程中非常重要，其中 β-catenin 的失调会激活 p53。在本研究中，我们以雌激素处理成骨细胞为范例，研究成骨细胞分化过程中两种蛋白质之间的关系。我们在短期测定中将成骨细胞样 ROS17/2.8 细胞暴露于 17-β 雌二醇 (E2)，并研究了 β-连环蛋白的细胞分布和表达。我们发现 E2 处理后 β-连环蛋白上调了几倍。 p53 的水平及其功能活性反映了 β-连环蛋白的数量变化。碱性磷酸酶是成骨细胞分化的早期标志物，其增加方式与 β-连环蛋白和 p53 类似。为了确定碱性磷酸酶表达和 β-连环蛋白之间是否存在直接关系，我们使用了两种不同的方法。在第一种方法中，用 LiCl 进行处理（已知 LiCl 可以激活 β-连环蛋白），导致碱性磷酸酶活性增加数倍。在第二种方法中，将野生型β-连环蛋白瞬时转染到成骨细胞中，使碱性磷酸酶活性增加两倍于基础水平，表明β-连环蛋白表达可以直接影响碱性磷酸酶表达。然而，β 连环蛋白活性的增加与其通过 TCF/LEF 介导的转录的信号传导活性的增加无关。 p53 和 β-catenin 定位的免疫荧光分析表明，E2 首先引起胞质 β-catenin 增加，随后 β-catenin 在细胞核中积累。在几个细胞中检测到核 p53 定位。 p53 的表达伴随着 β-连环蛋白分布到细胞质和细胞边界。两种蛋白均强烈染色的细胞亚群似乎已凋亡。这些结果表明 p53 和 β-catenin 信号通路之间的相互作用可能在成骨细胞分化和组织稳态维持中发挥关键作用。
This study was undertaken to examine the relationship between the tumor suppressor gene p53 and the nuclear signaling protein beta-catenin during bone differentiation. Cross talk between p53 and beta-catenin pathways has been demonstrated and is important during tumorigenesis and DNA damage, where deregulation of beta catenin activates p53. In this study, we used estrogen treatment of osteoblasts as a paradigm to study the relationship between the two proteins during osteoblast differentiation. We exposed osteoblast-like ROS17/2.8 cells to 17-beta estradiol (E2), in a short term assay, and studied the cellular distribution and expression of beta-catenin. We found beta-catenin to be up regulated several fold following E2 treatment. Levels of p53 and its functional activity mirrored the quantitative changes seen in beta-catenin. Alkaline phosphatase, an early marker of osteoblast differentiation, was increased in a manner similar to beta-catenin and p53. In order to determine if there was a direct relationship between alkaline phosphatase expression and beta-catenin, we used two different approaches. In the first approach, treatment with LiCl, which is known to activate beta-catenin, caused a several fold increase in alkaline phosphatase activity. In the second approach, transient transfection of wild type beta-catenin into osteoblasts increased alkaline phosphatase activity two fold over basal levels, showing that beta catenin expression can directly affect alkaline phosphatase expression. However increase in beta catenin activity was not associated with an increase in its signaling activity through TCF/LEF mediated transcription. Immunofluorescence analyses of p53 and beta-catenin localization showed that E2 first caused an increase in cytosolic beta-catenin followed by the accumulation of beta-catenin in the nucleus. Nuclear p53 localization was detected in several cells. Expression of p53 was accompanied by distribution of beta-catenin to the cytoplasm and cell borders. A sub population of cells staining strongly for both proteins appeared to be apoptotic. These results suggest that interactions between p53 and beta-catenin signaling pathways may play a key role in osteoblast differentiation and maintenance of tissue homeostasis.
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影响因子：
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通讯作者：
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