Correlated expression of matrix metalloproteinases and ets family transcription factor E1A-F in invasive oral squamous-cell-carcinoma-derived cell lines.

Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. Transcription regulatory regions of MMP genes often contain binding sites for ets transcription factors. We recently isolated a cDNA encoding human E1A-F, a member of the ets oncogene family, and showed that E1A-F can upregulate MMP genes by CAT assay. We attempted to investigate the relationship between E1A-F mRNA expression and MMP protein expression in four different types of oral squamous-cell-carcinoma-derived cell lines (HSC 3, SAS, KB, and Ca 9.22). HSC 3 and SAS are highly invasive cell lines when they are injected in the tongue of nude mice. Raft culture of HSC 3 and SAS revealed the same characteristics as seen in tumors implanted in vivo. Both type I collagenase (MMP-1) and 92-kd type IV collagenase (MMP-9) were detected in cultured HSC 3 and SAS cells. E1A-F mRNA was demonstrated to be highly expressed in HSC 3 and SAS by Northern blotting, and in situ hybridization confirmed E1A-F mRNA expression at the invasion front of tumor cells seeded on collagen gel. On the other hand, KB and Ca 9.22 have little potential for invasion, and MMP-1 and MMP-9 protein and E1A-F mRNA could not be detected. These results suggest that the ets-related E1A-F participates in the regulation of invasion-associated MMP genes and is involved in presenting invasive activity in tumor cells of oral squamous cell carcinoma.