Regulation of E-cadherin/catenin complex patterns by epidermal growth factor receptor modulation in human lung cancer cells

被引:38
作者
Al Moustafa, AE
Yen, L
Benlimame, N
Alaoui-Jamali, MA
机构
[1] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada
[2] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Dept Oncol, Montreal, PQ H3T 1E2, Canada
[3] McGill Univ, Ctr Translat Res Canc, Montreal, PQ H3T 1E2, Canada
[4] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada
关键词
E-cadherin/catenin complex; epidermal growth factor-receptor; lung cancer cells;
D O I
10.1016/S0169-5002(02)00025-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We previously demonstrated that a ligand-blocking monoclonal antibody (mAb) against the epidermal growth factor-receptor (EGF-R), LA1, induced morphological conversion from epithelial-like to epithelial of the human lung cancer cell line, H322. This was accompanied by an up-regulation of epithelial cadherin (E-cadherin) expression (Clin. Cancer Res. 5 (1999) 681). In the present paper, we show that mAb LA I induces the epithelial-like to epithelial conversion of the human lung cancer cell line, A549. In A549 and H322 cells, which express a detectable amount of EGF-R (ErbB-1), ErbB-2. ErbB-3, and ErbB-4 receptors, the LA1 mAb induces up-regulation of the E-cadherin/catenin complex (alpha-, beta- and gamma-catenins), This is associated with re-localization of E-cadherin, alpha-catenin, (and to a lesser extent beta-catenin), but not gamma-catenin. Additionally, we report that mAb LA1 inhibits cell motility. In contrast, epidermal growth factor (EGF) or heparin-binding EGF-like growth factor (HB-EGF) induces the epithelial-like to fibroblastoid conversion of A549 and H322 cell lines, slightly reduces the expression of E-cadherin and beta-catenin, but not alpha- and gamma-catenins, and stimulates cell motility. These Studies demonstrate that EGF-R modulation regulates the E-cadherin/catenin complex and cell motility in human lung epithelial carcinoma cells. Our results may have important therapeutic implications for the treatment of invasive human lung carcinomas via the restoration of the cadherin/catenin complex using inhibitors of EGF-R. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:49 / 56
页数:8
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