Synovial fibroblast-like cell transfection with the SV40 large T antigen induces a transformed phenotype and permits transient tumor formation in immunodeficient mice

J Rheumatol. 1994 Aug;21(8):1409-19.


Objective: To understand the intracellular signals leading to transformed-like growth of synovial fibroblast-like cells from patients with rheumatoid arthritis (RA).

Methods: Cell lines stably transfected with one or both of 2 complementary oncogenes, the SV40 large T antigen and the ras oncogene, were studied for phenotypic changes.

Results: Synovial fibroblast-like cells stably transfected with the SV40 large T antigen, but not the ras oncogene, showed high levels of growth factor independent proliferation, grew under anchorage independent conditions, expressed cathepsin L mRNA, and formed transient tumors in immunodeficient mice. Synovial fibroblast-like cells stably transfected with both oncogenes appeared phenotypically similar to synovial fibroblast-like cells transfected with the large T antigen alone.

Conclusion: The SV40 large T antigen confers a phenotype on synovial fibroblast-like cells similar to that stimulated by growth factors, suggesting that it stimulates the same intracellular signalling pathway leading to cytokine induced, transformed synovial fibroblast-like cell growth. When injected into immunodeficient mice these transfected cells formed tumors characterized by rapid, transient growth, central necrosis, and neutrophil infiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics*
  • Arthritis, Rheumatoid / pathology
  • Base Sequence
  • Cathepsin L
  • Cathepsins / genetics
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Collagenases / genetics
  • Cysteine Endopeptidases
  • DNA / analysis
  • DNA / genetics
  • Endopeptidases*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Genes, ras / genetics
  • Growth Substances / pharmacology
  • Mice
  • Mice, SCID
  • Molecular Sequence Data
  • Osteoarthritis / pathology
  • Phenotype
  • Plasmids / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*
  • Transfection / genetics*


  • Antigens, Polyomavirus Transforming
  • Growth Substances
  • RNA, Messenger
  • DNA
  • Cathepsins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Cathepsin L
  • Ctsl protein, mouse
  • Collagenases