E1AF Induces Both Matrix Metalloprotease Transcription and Cell Cycle Arrest that Occurs in the Stage of Cancer Cell Invasion

E1AF, an ets-oncogene family transcription factor, has been shown to upregulate transcription from matrix metalloproteinase (MMP) genes, which confers the invasive phenotype on cancer cells. On the other hand, we have demonstrated by luciferase assay that E1AF positively regulates transcription from the p21waf1/cip1 promoter. Ca9.22 cells were transfected with a metallothionein-inducible E1AF expression vector (Ca9.22MTF) to investigate the relationship between invasive ability and cell cycle modulation caused by E1AF. MMP-9 and p21waf1/cip1 protein were synergistically increased in the ZnCl2 stimulated CA9.22MTF cells, and both proteins were identified in the same cells when E1AF was induced. These results imply that invasive growth of tumor cells occurs in the static state of the cell cycle and that E1AF plays a key role in this phenomenon.