Direct transforming activity of TGF-beta on rat fibroblasts.
Treatment of NRK 536 fibroblasts with EGF and transforming growth factor type beta (TGF-beta) is known to lead to the reversible induction of the transformed phenotype in a large percentage of cells. Maintenance of the transformed state is dependent on the continuous presence of the cytokines. Here we show that treatment of these cells with TGF-beta alone leads to the formation of a small percentage of colonies, the majority of which stably retain the transformed phenotype after removal of the cytokine. Colony induction is dependent on the concentration of TGF-beta originally present. Stably transformed cells grow in soft agar without further addition of exogenous TGF-beta, and exhibit criss-cross morphology in monolayer culture and a diffuse actin pattern. Transformation of NRK 536 cells can be demonstrated only for individualized cells treated with TGF-beta in soft agar, as treatment in monolayer leads to the induction of apoptosis in newly transformed cells by neighboring normal cells. Transformation of NRK 536 fibroblasts by TGF-beta is not due to the induction of point mutations by TGF-beta.
Vossbeck
H
H
Abteilung Virologie, Universität Freiburg, Germany.
Strahm
B
B
Höfler
P
P
Bauer
G
G
D000362:Agar; D000818:Animals; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype; D017354:Point Mutation; D051381:Rats; D013234:Stem Cells / Q000187:drug effects; D014170:Transformation, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D000362:Agar