E1AF expression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters

Oncol Rep. 2005 Apr;13(4):715-20.

Abstract

E1AF is an ets-oncogene family transcription factor that has been shown to up-regulate multiple MMPs whereas MMP-2, a potent extracellular matrix degrading enzyme, is not up-regulated. We investigated the activation mechanism of MMP-2 in oral squamous cell carcinoma. Chloramphenicol acetyltransferase (CAT) assay was utilized to investigate whether E1AF is able to up-regulate membrane type-1 matrix metalloproteinase (MT1-MMP), which is known to activate MMP-2. Expression of the CAT reporter gene under the control of the MT1-MMP promoter was increased approximately 40-fold by co-transfection with the E1AF expression vector. Real-time RT-PCR study was carried out in 25 patients with tongue squamous cell carcinoma, and the mRNA expression level of E1AF and MT1-MMP was synergistically increased. These results indicate that E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2 into active-MMP-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus E1A Proteins / biosynthesis*
  • Adult
  • Aged
  • Biopsy
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Chloramphenicol O-Acetyltransferase / metabolism
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors
  • Humans
  • Male
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phenotype
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-ets
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tongue Neoplasms / pathology*
  • Up-Regulation

Substances

  • Adenovirus E1A Proteins
  • DNA, Complementary
  • ETV4 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • RNA
  • Chloramphenicol O-Acetyltransferase
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases