4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis
4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis
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DOI：
10.1158/1078-0432.ccr-06-1560
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发表时间：
2007-01-01
影响因子：
11.5
通讯作者：
Ramon y Cajal, Santiago
中科院分区：
文献类型：
--
作者：
Rojo, Federico;Najera, Laura;Ramon y Cajal, Santiago
目的：细胞信号通路包括从细胞膜到细胞核的复杂的无数相互关联的因子，如erbB家族受体和磷酸肌苷-3激酶/Akt/mTOR和Ras-Raf-ERK级联，它们驱动增殖信号，促进生存，调节蛋白质合成。实验设计：为了找到这些通路中的关键因素，提供恶性肿瘤的预后信息，我们研究了103例人类乳腺肿瘤的免疫组织化学谱，包括总蛋白和磷酸化(p)蛋白：人表皮生长因子受体2 （HER2）、表皮生长因子受体、细胞外信号调节激酶1/2、Akt、4E结合蛋白1 （4EBP1）、真核起始因子4E、磷酸化核糖体蛋白S6激酶1、磷酸化核糖体蛋白S6和Ki67。Western blot和反向裂解蛋白阵列也在肿瘤亚群中进行。结果：在高比例（41.9%）的肿瘤中检测到磷酸肌醇-3激酶/Akt/mTOR级联的激活。HER2过表达肿瘤的P - akt水平高于阴性肿瘤(P
Purpose: Cell signaling pathways include a complex myriad of interconnected factors from the membrane to the nucleus, such as erbB family receptors and the phosphoinositide-3-kinase/Akt/mTOR and Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, and regulate protein synthesis.Experimental Design: To find pivotal factors in these pathways, which provide prognostic information in malignancies, we studied 103 human breast tumors with an immunohistochemical profile, including total and phosphorylated (p) proteins: human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1 (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6 kinase 1, phosphorylated ribosomal protein S6, and Ki67. Western blot and reverse lysate protein arrays were also done in a subset of tumors.Results: Significantly, activation of the phosphoinositide-3-kinase/Akt/mTOR cascade was detected in a high proportion of tumors (41.9%). Tumors with HER2 overexpression showed higher p-Akt as compared with negative tumors (P