Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines
Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines
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DOI：
10.1038/sj.onc.1204920
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发表时间：
2001-11-01
期刊：
影响因子：
8
通讯作者：
Yee, D
中科院分区：
文献类型：
--
作者：
Jackson, JG;Zhang, XH;Yee, D
胰岛素样生长因子（IGFs）调节乳腺癌细胞增殖，保护细胞免于凋亡，并促进转移。在这项研究中，我们研究了IGF信号通路在两个乳腺癌细胞系选择的转移行为。选择LCC 6作为来自亲本MDA-MB-435细胞（435 P）的无胸腺小鼠中的腹水肿瘤生长。MDA-231 BO细胞系来源于无胸腺小鼠心内注射MDA-MB-231细胞系后形成的骨转移。与亲本细胞Rues相比，IGF-I处理增强了转移性变体中IRS-2的磷酸化。IGF-I刺激了变异细胞的细胞迁移，但在亲本细胞中没有。到.为了确定IRS-2在IGF介导的运动中的作用，我们用反义IRS-2构建体转染MDA-231 BO细胞。转染细胞的IRS-2水平降低。与对照细胞相比，IGF介导的运动性和非锚定依赖性生长减弱。然而，粘附纤维连接蛋白。与MDA-231 BO细胞相比，在转染细胞中增强。我们的数据显示，选择用于体内转移行为的乳腺癌细胞具有增加的IRS-2活化和信号传导。在这些细胞中，IGF-I增强细胞粘附和运动性，表明IRS-2可能介导恶性表型的这些方面。
Insulin-like growth factors (IGFs) regulate breast cancer cell proliferation, protect cells from apoptosis, and enhance metastasis. In this study, we examined the IGF signaling pathway in two breast cancer cell lines selected for metastatic behavior. LCC6 was, selected for growth as, an ascites tumor in athymic mice from parental MDA-MB-435 cells (435P). The MDA-231BO cell line was derived from osseous metastases that formed after intracardiac injection of the MDA-MB-231 cell line in athymic mice. Compared to the parental cell Rues, IGF-I treatment enhanced IRS-2 phosphorylation over IRS-I in the metastatic variants. IGF-I stimulated cell migration in the variant cells, but not in the parental cells. To. determine the role for IRS-2 in IGF-mediated motility, we transfected MDA-231BO cells with, an anti-sense IRS-2 construct. Transfected cells had decreased levels of IRS-2. with diminished IGF-mediated motility and anchorage independent growth when compared to control cells. However, adherence to fibronectin was. enhanced in the transfected cells compared to MD A-231BO cells. Our data show that breast cancer cells selected for metastatic behavior in vivo have increased IRS-2 activation and signaling. In these cells, IGF-I enhances cell adhesion and motility suggesting that IRS-2 may mediate these aspects of the malignant phenotype.