Proteomic analysis reveals that 14-3-3σ is down-regulated in human breast cancer cells

Proteomic analysis reveals that 14-3-3σ is down-regulated in human breast cancer cells
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发表时间:
2001
期刊:
影响因子:
11.2
通讯作者:
A. Vercoutter‐Edouart;J. Lemoine;X. Bourhis;H. Louis;B. Boilly;V. Nurcombe;F. Révillion;J. Peyrat-J.-Peyr
A. Vercoutter‐Edouart;J. Lemoine;X. Bourhis;H. Louis;B. Boilly;V. Nurcombe;F. Révillion;J. Peyrat-J.-Peyr
中科院分区:
医学1区
文献类型:
--
作者:
A. Vercoutter‐Edouart;J. Lemoine;X. Bourhis;H. Louis;B. Boilly;V. Nurcombe;F. Révillion;J. Peyrat-J.-Peyr

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被称为14-3-3的一类分子伴侣通过其对各种信号传导途径(包括Raf/促分裂原活化蛋白激酶途径)的明显调节而参与细胞生长的控制。在乳腺癌细胞中,14-3-3的σ形式已被证明与细胞周期蛋白依赖性激酶相互作用,并控制进入有丝分裂的速率。为了测试14-3-3在乳腺上皮细胞瘤形成中的直接作用,我们使用基于二维电泳和基质辅助激光解吸/电离质谱(MALDI-TOF)的蛋白质组学方法定量了14-3-3蛋白水平。我们在这里显示,与正常乳腺上皮细胞相比,14-3-3σ蛋白在原型乳腺癌细胞系MCF-7和MDA-MB-231以及原发性乳腺癌中强烈下调。相比之下,14-3-3的α、β、δ或γ亚型的水平在正常和转化细胞中是相同的。数据支持14-3-3σ由于其作为肿瘤抑制因子的作用而参与乳腺上皮细胞的肿瘤转化的观点;因此,它可以构成对该病理具有临床疗效的稳健标志物。
The class of molecular chaperones known as 14-3-3 is involved in the control of cellular growth by virtue of its apparent regulation of various signaling pathways, including the Raf/mitogen-activated protein kinase pathway. In breast cancer cells, the σ form of 14-3-3 has been shown to interact with cyclin-dependent kinases and to control the rate of entry into mitosis. To test for a direct role for 14-3-3 in breast epithelial cell neoplasia, we have quantitated 14-3-3 protein levels using a proteomic approach based on two-dimensional electrophoresis and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF). We show here that 14-3-3σ protein is strongly down-regulated in the prototypic breast cancer cell lines MCF-7 and MDA-MB-231 and in primary breast carcinomas as compared with normal breast epithelial cells. In contrast, levels of the α, β,δ , or ζ isoforms of 14-3-3 were the same in both normal and transformed cells. The data support the idea that 14-3-3σ is involved in the neoplastic transition of breast epithelial cells by virtue of its role as a tumor suppressor; as such, it may constitute a robust marker with clinical efficacy for this pathology.