Enhanced invasive properties of rat embryo fibroblasts transformed by adenovirus E1A mutants with deletions in the carboxy-terminal exon

Oncogene. 1992 Mar;7(3):439-43.

Abstract

E1A genes deficient in the carboxy-terminal exon can cooperate with activated ras oncogenes to induce transformation of rat embryo fibroblasts. However, the resulting transformed foci show a distinct appearance characterized by a decreased adhesion of the cells to the substrate. Here, we demonstrate that cell lines derived from foci showing the variant morphology are defective in down-regulation of stromelysin 1 metalloprotease expression and show an increased invasive propensity compared with cells transformed by wild-type E1A. The altered focus morphology, the high invasive propensity and the elevated stromelysin 1 expression were abrogated by glucocorticoid treatment. Our results show that E1A functions necessary for transformation and inhibition of invasive properties may be separated, and indicate that a 23 amino acid serine/threonine-rich region within the E1A carboxy-terminal exon is required for efficient repression of metalloprotease expression in transformed cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Early Proteins
  • Animals
  • Cell Adhesion
  • Cell Transformation, Neoplastic / pathology
  • Cell Transformation, Viral*
  • Cells, Cultured
  • DNA Mutational Analysis
  • Gene Expression
  • In Vitro Techniques
  • Matrix Metalloproteinase 3
  • Metalloendopeptidases / genetics
  • Oncogene Proteins, Viral / genetics*
  • Oncogenes
  • RNA, Messenger / genetics
  • Rats
  • Recombinant Proteins

Substances

  • Adenovirus Early Proteins
  • Oncogene Proteins, Viral
  • RNA, Messenger
  • Recombinant Proteins
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3