2 TRANSCRIPTION FACTORS, E1AF AND N-MYC, CORRELATE WITH THE INVASIVENESS OF NEUROBLASTOMA CELL-LINES

The ets transcription factor E1AF can activate several matrix-degradin g metalloproteinase (MMP) genes and is implicated in enhancement of tu mor cell invasion. Here we compared the invasive activity of five huma n neuroblastoma cell lines (TGW, GOTO, SK-N-BE, SK-N-SH and SK-N-AS), which exhibit distinct levels of N-myc amplification, together with th e expression of E1AF. Extracellular matrix-degrading proteases and the ir inhibitor proteins, which play an important role in local invasion, were also analyzed. The activity to invade through reconstituted base ment membrane was high in cells (TGW, GOTO, and SK-N-BE) with N-myc am plification, and these cells produced relatively large amounts of E1AF mRNA, correlating with the invasive activities. Of several matrix met alloproteinases (MMPs) and a tissue inhibitor of MMPs (TIMP), only mem brane-bound type 1 MMP (MT1-MMP) was specifically detected in N-myc-am plified cells, suggesting a role of MT1-MMP in neuroblastoma cell inva sion. MMP-2 (72 kD type IV collagenase), TIMP-1 and TIMP-2 were expres sed in all five cell lines. Urokinase-type plasminogen activator was u ndetectable. These findings indicate that the transcription factors E1 AF and N-myc are related to malignant phenotypes of neuroblastoma.