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


CONCLUSIONS
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.
Lemaire
R
R
Centre d'Immunologie et de Biologie Parasitaire, Unité mixte INSERM U167, CNRS U624, Institut Pasteur de Lille, France.
Flipo
R M
RM
Monté
D
D
Dupressoir
T
T
Duquesnoy
B
B
Cesbron
J Y
JY
Janin
A
A
Capron
A
A
Lafyatis
R
R
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000473:pathology; D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics; D003546:Cysteine Endopeptidases; D004247:DNA / Q000032:analysis / Q000235:genetics; D010450:Endopeptidases; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D011905:Genes, ras / Q000235:genetics; D006133:Growth Substances / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000473:pathology; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D014162:Transfection / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D006133:Growth Substances; D012333:RNA, Messenger; D004247:DNA; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D017364:Collagenases