BAG-1可加速人胃癌细胞的细胞运动。

BAG-1 accelerates cell motility of human gastric cancer cells.

作者信息

Naishiro Y, Adachi M, Okuda H, Yawata A, Mitaka T, Takayama S, Reed J C, Hinoda Y, Imai K

机构信息

First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.

出版信息

Oncogene. 1999 May 27;18(21):3244-51. doi: 10.1038/sj.onc.1202661.

DOI:10.1038/sj.onc.1202661

PMID:10359530

Abstract

BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of human gastric cancer cells. Two independent in vitro migration assays showed that the BAG-1-expressing MKN74 cells exhibited more active migration compared with control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor migration responses to HGF. The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. In BAG-1 transfected gastric cancer MKN74 cells, BAG-1 colocalized with cytokeratin as well as actin filaments, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA). Taken together, these studies demonstrate that BAG-1 has a novel function as promoter of cell migration in human gastric cancer cells, possibly through cooperation with cytoskeletal proteins.

摘要

BAG-1是一种与Hsp70/Hsc70结合的蛋白质，它能与Bcl-2、Raf-1、类固醇激素受体、Siah-1以及肝细胞生长因子（HGF）受体相互作用，这表明BAG-1蛋白具有多种功能。在此，我们提供证据表明，基因转移介导的BAG-1过表达显著增强了人胃癌细胞的运动能力。两项独立的体外迁移试验表明，与对照转染细胞或亲本MKN74细胞相比，表达BAG-1的MKN74细胞表现出更活跃的迁移。在MKN74细胞中，BAG-1的过表达既不影响细胞黏附能力，也不影响对HGF的迁移反应。在另一人胃癌MKN45细胞系的转染细胞中也同样观察到BAG-1对细胞迁移的促进作用。在转染了BAG-1的胃癌MKN74细胞中，BAG-1与细胞角蛋白以及肌动蛋白丝共定位，并集中在溶血磷脂酸（LPA）诱导的膜皱襞处。综上所述，这些研究表明BAG-1在人胃癌细胞中具有作为细胞迁移促进因子的新功能，可能是通过与细胞骨架蛋白协同作用实现的。