Novel Breast Cancer Metastasis-Associated Proteins
Novel Breast Cancer Metastasis-Associated Proteins
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DOI：
10.1021/pr8007368
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发表时间：
2009-02-01
影响因子：
4.4
通讯作者：
Lim, Yoon-Pin
中科院分区：
文献类型：
--
作者：
Ho, Jiapei;Kong, Jacklyn-Wai-Fun;Lim, Yoon-Pin
通过使用包含四种等基因细胞系的乳腺癌转移模型，采用基于iTRAQ的ESI-LC/MS/MS蛋白质组学来对随着癌细胞获得增加的转移潜力而发生的蛋白质表达变化进行编目。从检测到的1000多种蛋白质中，197种蛋白质，包括药物靶向激酶、磷酸酶、蛋白酶和转录因子，在癌细胞变得更具转移性时显示出差异表达。总体而言，蛋白质表达变化的数量均匀分布在轻度（类似于30%）、中度（类似于40%）和侵袭性（类似于30%）转移性癌细胞中。一些变化被发现是特定的一个，而其他的两个或更多的表型所需的。KEGG Orthology表明细胞代谢中的主要重编程，以及遗传和环境信息处理中的较小程度。鉴定了10种新的转移相关蛋白，并验证了7种蛋白的基于iTRAQ的表达谱与基于抗体的方法一致。使用包含50个浸润性和转移性病变的匹配病例的组织微阵列，证实在原位癌向浸润性和转移性癌的临床进展期间，SH 3GLB 1和SUB 1、SND 1、TRIM 28的表达谱分别下调和上调。我们的研究揭示了蛋白质组分子畸变和乳腺癌转移的潜在新参与者。
With the use of the breast cancer metastatic model, which comprises four isogenic cell lines, iTRAQ-based ESI-LC/MS/MS proteomics was employed to catalog protein expression changes as cancer cells acquire increasing metastatic potential. From more than 1000 proteins detected, 197 proteins, including drug-targetable kinases, phosphatases, proteases and transcription factors, displayed differential expression when cancer cells becomes more metastatic. Overall, the number of protein expression changes was evenly distributed across mildly (similar to 30%), moderately (similar to 40%) and aggressively (similar to 30%) metastatic cancer cells. Some changes were found to be specific to one while others were required for two or more phenotypes. KEGG Orthology suggests major reprogramming in cell metabolism and to smaller extents in genetic and environmental information processing. Ten novel metastasis-associated proteins were identified and the iTRAQ-based expression profiles of 7 proteins were verified to be congruent with antibody-based methods. With the use of tissue microarrays comprising 50 matched cases of invasive and metastatic lesions, the expression profiles of SH3GLB1 and SUB1, SND1, TRIM28 were validated to be down- and up-regulated, respectively, during clinical progression of carcinoma in situ to invasive and metastatic carcinomas. Our study has unraveled proteome-wide molecular aberrations and potentially new players in breast cancer metastasis.