Proteomic consequences of a single gene mutation in a colorectal cancer model.
Proteomic consequences of a single gene mutation in a colorectal cancer model.
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DOI：
10.1021/pr2009109
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发表时间：
2012-02-03
影响因子：
4.4
通讯作者：
Slebos, Robbert J. C.
中科院分区：
文献类型：
--
作者：
Halvey, Patrick J.;Zhang, Bing;Coffey, Robert J.;Liebler, Daniel C.;Slebos, Robbert J. C.
关键词：
特定癌症相关突变的蛋白质组效应尚未得到很好的表征。在结直肠癌（CRC）中，关键信号通路中相对少量的突变似乎驱动肿瘤发生。大肠腺瘤性息肉病（APC）是Wnt信号的负调节因子，在多达60%的结直肠癌肿瘤中发生突变。在这里，我们通过使用异位恢复野生型APC表达的等基因CRC细胞培养模型来研究单基因突变的蛋白质组学后果。利用LC-MS /MS无标签散弹枪蛋白组学技术，在SW480Null（突变型APC）和SW480APC（恢复型APC）中鉴定出5000多个蛋白。我们观察到155个蛋白在两种细胞系之间有显著的表达差异，其中26个蛋白的表达趋势与基因表达测量相反。蛋白质变化与APCNull表型的先前特征相对应：细胞粘附蛋白的缺失，细胞周期调节因子的增加，Wnt信号相关蛋白的改变以及β-catenin的重新分布。SW480Null细胞中RNA加工蛋白和类异戊二烯生物合成蛋白的表达增加。因此，霰弹枪蛋白质组学揭示了与单个基因变化相关的蛋白质组学差异，包括许多落在已知靶途径之外的新差异。特定癌症相关突变的蛋白质组效应尚未得到很好的表征。在结直肠癌（CRC）中，关键信号通路中相对少量的突变似乎驱动肿瘤发生。大肠腺瘤性息肉病（APC）是Wnt信号的负调节因子，在多达60%的结直肠癌肿瘤中发生突变。在这里，我们研究了单个基因突变的蛋白质组学后果。霰弹枪蛋白质组学揭示了与单个基因变化相关的蛋白质组学差异，包括许多落在已知靶途径之外的新差异。
The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signaling, occur in up to 60% of CRC tumors. Here we examine the proteomic consequences of a single gene mutation by using an isogenic CRC cell culture model in which wildtype APC expression has been ectopically restored. Using LC–MS/MS label free shotgun proteomics, over 5000 proteins were identified in SW480Null (mutant APC) and SW480APC (APC restored). We observed 155 significantly differentially expressed proteins between the two cell lines, with 26 proteins showing opposite expression trends relative to gene expression measurements. Protein changes corresponded to previously characterized features of the APCNull phenotype: loss of cell adhesion proteins, increase in cell cycle regulators, alteration in Wnt signaling related proteins, and redistribution of β-catenin. Increased expression of RNA processing and isoprenoid biosynthetic proteins occurred in SW480Null cells. Therefore, shotgun proteomics reveals proteomic differences associated with a single gene change, including many novel differences that fall outside known target pathways. The proteomic effects of specific cancer-related mutations have not been well characterized. In colorectal cancer (CRC), a relatively small number of mutations in key signaling pathways appear to drive tumorigenesis. Mutations in adenomatous polyposis coli (APC), a negative regulator of Wnt signaling, occur in up to 60% of CRC tumors. Here we examine the proteomic consequences of a single gene mutation. Shotgun proteomics reveals proteomic differences associated with a single gene change, including many novel differences that fall outside known target pathways.
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