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-sm all-cell lung cancers (NSCLCs). We have previously reported that EIAF, a me mber of the Ets-related transcription factor family, confers invasive pheno type on breast cancer and oral squamous-cell carcinoma cell lines. In our s tudy, we analyzed the EIAF expression in cell lines and resected tumors of NSCLCs by Northern blot and in situ hybridization analyses and found that 1 5 of 17 cell lines and 12 of 19 tumors expressed EIAF mRNA while normal lun g tissue and concomitant normal cells within tumors did not. To examine the biologic importance of EIAF in NSCLCs, we introduced the EIAF gene into VM RC-LCD and NCI-H226 NSCLC cell lines lacking EIAF expression, and examined cell motility and invasion activities. EIAF-transfected VMRC-LCD cells show ed increased cell motility that was 2-fold that of parental and vector-tran sfected 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 f actor (HGF), which is one of the most effective cell-scattering factors, st imulated the motile and invasive activities in EIAF-transfected VMRC-LCD an d NCI-H226 cells but not in their parental or vector-transfected control ce lls. Ets-1 mRNA expression was found in EIAF-transfected VMRC-LCD cells but not in parental or vector-transfected cells. HGF further induced expressio n of the Ets-1 and urokinase-type plasminogen activator (uPA) genes specifi cally in EIAF-transfected cells. These findings suggest that EIAF plays a s ubstantial role in the cell motility and invasion of NSCLCs. (C) 2001 Wiley -Liss, Inc.