Egfr Over-Expression And Mutations Lead To A Change In Biological Characteristics Of Human Lung Adenocarcinoma Cells

Brain metastasis (BM) is a frequent occurrence from lung cancer, and is associated with an overall poor prognosis. Accumulating evidence has demonstrated a high incidence of BM in lung adenocarcinoma patients with the epidermal growth factor receptor (EGFR) mutation. To investigate the potential molecular mechanisms, we constructed EGFR over-expression and three EGFR-mutant (EGFR-L858R, EGFR-E746-A750del and EGFR-T790M) human lung adenocarcinoma cell sublines by using lentiviral transfection of NCI-H1563 cells. The effects of EGFR over-expression and mutations on proliferation, migration, and invasion in vitro were investigated. Herein, we found that EGFR over-expression and the EGFR-E746-A750del (19 exon deletion) mutation significantly enhanced cellular proliferation, migration, and invasion. Moreover, the expression of BM-associated genes, such as matrix metalloproteinase-9 (MMP-9), vascular epithelial growth factor (VEGF), and S100 beta, was significantly increased in both EGFR over-expression and EGFR-E746-A750del mutated cell sublines. Therefore, our study demonstrates that EGFR overexpression and the 19 exon deletion mutation could enhance cellular invasion and even promote the occurrence of BM, possibly by up-regulating the expression of MMP-9, VEGF, and S100 beta.