Expression in rat fibroblasts of a human transforming growth factor-alpha cDNA results in transformation.
Acquisition of the ability to produce and respond to a growth factor may result in increased cellular proliferation and could lead to malignant transformation. The fact that a large variety of tumor cells secrete transforming growth factor-alpha (TGF-alpha) suggests involvement of TGF-alpha in cellular transformation and provides supporting evidence for the autocrine stimulation model. In order to determine directly the role of TGF-alpha in tumorigenicity, we introduced a human TGF-alpha cDNA expression vector into established nontransformed Fischer rat fibroblast (Rat-1) cells. Synthesis and secretion of human TGF-alpha by these cells results in the loss of anchorage-dependent growth and induces tumor formation in nude mice. Anti-human TGF-alpha monoclonal antibodies prevent TGF-alpha expressing Rat-1 cells from forming colonies in soft agar.
Rosenthal
A
A
Lindquist
P B
PB
Bringman
T S
TS
Goeddel
D V
DV
Derynck
R
R
D000818:Animals; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000502:physiology; D010455:Peptides / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D015291:Transforming Growth Factors
D006133:Growth Substances; D009363:Neoplasm Proteins; D010455:Peptides; D015291:Transforming Growth Factors; D004247:DNA