Proteomic characterization of Her2/neu-overexpressing breast cancer cells.
Proteomic characterization of Her2/neu-overexpressing breast cancer cells.
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DOI：
10.1002/pmic.201000297
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发表时间：
2010-11
期刊：
影响因子：
3.4
通讯作者：
Pandey, Akhilesh
中科院分区：
文献类型：
--
作者：
Chen, Hexin;Pimienta, Genaro;Gu, Yiben;Sun, Xu;Hu, Jianjun;Kim, Min-Sik;Chaerkady, Raghothama;Gucek, Marjan;Cole, Robert N.;Sukumar, Saraswati;Pandey, Akhilesh
受体酪氨酸激酶 HER2 是一种在浸润性乳腺癌中扩增的癌基因，其在乳腺上皮细胞系中的过度表达是致瘤表型的重要决定因素。因此，HER2 过表达的乳腺肿瘤通常表明患者预后不良。一些定量蛋白质组学研究采用了二维凝胶电泳与串联质谱法相结合，这仅提供了有关 HER2/neu 信号传导分子机制的有限信息。在本研究中，我们使用基于 SILAC 的方法来比较正常乳腺上皮细胞与 Her2/neu 过表达乳腺上皮细胞的蛋白质组谱，后者是从 MMTV-Her2/neu 转基因小鼠中产生的原发性乳腺肿瘤中分离出来的。我们鉴定了 23 种在乳腺癌中具有相关注释功能的蛋白质，显示出显着的差异表达。这包括肌酸激酶、视黄醇结合蛋白 1、胸腺素 β 4 和肿瘤蛋白 D52 的过度表达，它们与 Her2 过度表达细胞的致瘤表型相关。凝溶胶蛋白和视黄醇结合蛋白1这两个基因的差异表达模式在正常和肿瘤组织中得到了进一步验证。最后，对已发表的癌症微阵列数据集进行的计算机分析揭示了 23 个基因特征，可用于预测乳腺癌患者无转移生存的概率。
The receptor tyrosine kinase HER2 is an oncogene amplified in invasive breast cancer and its overexpression in mammary epithelial cell lines is a strong determinant of a tumorigenic phenotype. Accordingly, HER2-overexpressing mammary tumors are commonly indicative of a poor prognosis in patients. Several quantitative proteomic studies have employed two-dimensional gel electrophoresis in combination with tandem mass spectrometry, which provides only limited information about the molecular mechanisms underlying HER2/neu signaling. In the present study, we used a SILAC-based approach to compare the proteomic profile of normal breast epithelial cells with that of Her2/neu-overexpressing mammary epithelial cells, isolated from primary mammary tumors arising in MMTV-Her2/neu transgenic mice. We identified 23 proteins with relevant annotated functions in breast cancer, showing a substantial differential expression. This included overexpression of creatine kinase, retinol-binding protein 1, thymosin beta 4 and tumor protein D52, which correlated with the tumorigenic phenotype of Her2-overexpressing cells. The differential expression pattern of two genes, gelsolin and retinol binding protein 1, was further validated in normal and tumor tissues. Finally, an in silico analysis of published cancer microarray datasets revealed a 23-gene signature which can be used to predict the probability of metastasis-free survival in breast cancer patients.
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