Dissection of signaling pathways in fourteen breast cancer cell lines using reverse-phase protein lysate microarray
Dissection of signaling pathways in fourteen breast cancer cell lines using reverse-phase protein lysate microarray
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DOI：
10.1177/153303460600500601
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发表时间：
2006-12-01
影响因子：
2.8
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Akkiprik, Mustafa;Nicorici, Daniel;Zhang, Wei
信号转导通路在乳腺癌的发生、发展和对不同疗法的反应中起着至关重要的作用。乳腺癌治疗中的一个主要问题是临床前研究中常用的不同肿瘤类型和细胞系之间的异质性。为了表征一些常用的乳腺癌细胞系的信号通路，并剖析许多通路与乳腺癌发展中的一些关键遗传和分子事件之间的关系，如p53突变，ErbB 2表达，雌激素受体（ER）/孕激素受体（PR）状态，我们使用蛋白质裂解物，用53种特异性抗体测量40种不同细胞信号蛋白的表达和磷酸化状态，阵表达数据的聚类分析显示，在所有细胞系中，磷脂酰肌醇3-激酶、Akt、哺乳动物雷帕霉素靶蛋白（mTOR）、Src和血小板衍生生长因子受体β（PDGFR β）都有紧密的聚类。ER和PR阳性乳腺细胞与ER和PR阴性乳腺细胞之间最差异表达的蛋白质是mTOR、Akt（pThr 308）、PDGFR β、PDGFR β（pTyr 751）、panSrc、Akt（pSer 473）、胰岛素样生长因子结合蛋白5（IGFBP 5）、Src（pTyr 418）、mTOR（pSer 2448）和IGFBP 2。许多凋亡蛋白如凋亡诱导因子、IGFBP 3、bad、bax和切割的caspase 9在携带突变型p53的乳腺癌细胞中过表达。己糖激酶同功酶1、ND 2和c-kit是ErbB 2高表达和低表达乳腺癌细胞中最差异表达的蛋白质。这项研究表明，ER/PR状态，ErbB 2表达和p53状态是影响下游信号通路的主要分子。
Signal transduction pathways play a crucial role in breast cancer development, progression, and response to different therapies. A major problem in breast cancer therapy is the heterogeneity among different tumor types and cell lines commonly used in preclinical studies. To characterize the signaling pathways of some of the commonly used breast cancer cell lines and dissect the relationship among a number of pathways and some key genetic and molecular events in breast cancer development, such as p53 mutation, ErbB2 expression, and estrogen receptor (ER)/progesterone receptor (PR) status, we performed pathway profiling of 14 breast cancer cell lines by measuring the expression and phosphorylation status of 40 different cell signaling proteins with 53 specific antibodies using a protein lysate array. Cluster analysis of the expression data showed that there was close clustering of phosphatidylinositol 3-kinase, Akt, mammalian target of rapamycin (mTOR), Src, and platelet-derived growth factor receptor beta (PDGFR beta) in all of the cell lines. The most differentially expressed proteins between ER- and PR-positive and ER- and PR-negative breast cells were mTOR, Akt (pThr308), PDGFR beta, PDGFR beta (pTyr751), panSrc, Akt (pSer473), insulin-like growth factor-binding protein 5 (IGFBP5), Src (pTyr418), mTOR (pSer2448), and IGFBP2. Many apoptotic proteins, such as apoptosis-inducing factor, IGFBP3, bad, bax, and cleaved caspase 9, were overexpressed in mutant p53-carrying breast cancer cells. Hexokinase isoenzyme 1, ND2, and c-kit were the most differentially expressed proteins in high and low ErbB2-expressing breast cancer cells. This study demonstrated that ER/PR status, ErbB2 expression, and p53 status are major molecules that impact downstream signaling pathways.