Regulation of E-cadherin/catenin complex patterns by epidermal growth factor receptor modulation in human lung cancer cells.
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 LA1 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.
Al Moustafa
Ala-Eddin
AE
Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Departments of Medicine and Oncology, and McGill Center for Translational Research in Cancer, Montreal, Que., Canada H3T 1E2. aalmoust@ldi.jgh.mcgill.ca
Yen
Lily
L
Benlimame
Naciba
N
Alaoui-Jamali
Moulay A
MA
D000911:Antibodies, Monoclonal; D015820:Cadherins / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma / Q000473:pathology*; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000494:pharmacology; D051180:Desmoplakins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000473:pathology*; D015534:Trans-Activators / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
D000911:Antibodies, Monoclonal; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D008024:Ligands; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin