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

Am J Pathol. 1996 Mar;148(3):693-700.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Extracellular Matrix / metabolism*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Metalloendopeptidases / metabolism*
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Transcription Factors
  • Metalloendopeptidases