Vercoutter-Edouart A S, Lemoine J, Le Bourhis X, Louis H, Boilly B, Nurcombe V, Révillion F, Peyrat J P, Hondermarck H
Equipe Facteurs de Croissance, Laboratoire de Biologie du Développement, UPRES-EA 1033, Villeneuve d'Ascq, France.
Cancer Res. 2001 Jan 1;61(1):76-80.
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 sigma 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 14-3-3sigma 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 alpha, beta, delta, or zeta isoforms of 14-3-3 were the same in both normal and transformed cells. The data support the idea that 14-3-3sigma 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.
被称为14-3-3的分子伴侣家族通过对包括Raf/丝裂原活化蛋白激酶途径在内的各种信号通路的明显调控，参与细胞生长的控制。在乳腺癌细胞中，已证明14-3-3的σ形式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在乳腺上皮细胞肿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）的蛋白质组学方法对14-3-3蛋白水平进行了定量。我们在此表明，与正常乳腺上皮细胞相比，在典型乳腺癌细胞系MCF-7和MDA-MB-231以及原发性乳腺癌中，14-3-3σ蛋白强烈下调。相反，14-3-3的α、β、δ或ζ亚型在正常细胞和转化细胞中的水平相同。这些数据支持这样一种观点，即14-3-3σ凭借其作为肿瘤抑制因子的作用参与乳腺上皮细胞的肿瘤转化；因此，它可能构成一种对这种病理具有临床疗效的可靠标志物。
