Expression of E1AF/PEA3, an ETS-related transcription factor in human non-small-cell lung cancers: Its relevance in cell motility and invasion

Cell invasion and metastasis characterize the malignant potential of non-small-cell lung cancers (NSCLCs). We have previously reported that EIAF, a member of the Ets-related transcription factor family, confers invasive phenotype on breast cancer and oral squamous-cell carcinoma cell lines. In our study, we analyzed the EIAF expression in cell lines and resected tumors of NSCLCs by Northern blot and in situ hybridization analyses and found that 15 of 17 cell lines and 12 of 19 tumors expressed EIAF mRNA while normal lung tissue and concomitant normal cells within tumors did not. To examine the biologic importance of EIAF in NSCLCs, we introduced the EIAF gene into VMRC-LCD and NCI-H226 NSCLC cell lines lacking EIAF expression, and examined cell motility and invasion activities. EIAF-transfected VMRC-LCD cells showed increased cell motility that was 2-fold that of parental and vector-transfected control cells (p < 0.01), and both cell motility and invasion were increased 1.6-fold in NCI-H226 (p < 0.01). Furthermore, hepatocyte growth factor (HGF), which is one of the most effective cell-scattering factors, stimulated the motile and invasive activities in EIAF-transfected VMRC-LCD and NCI-H226 cells but not in their parental or vector-transfected control cells. Ets-1 mRNA expression was found in EIAF-transfected VMRC-LCD cells but not in parental or vector-transfected cells. HGF further induced expression of the Ets-1 and urokinase-type plasminogen activator (uPA) genes specifically in EIAF-transfected cells. These findings suggest that EIAF plays a substantial role in the cell motility and invasion of NSCLCs. (C) 2001 Wiley-Liss, Inc.