Transforming growth factor beta stimulates mitogenically mouse NIH3T3 fibroblasts and those cells transformed by the EJ-H ras oncogene.
TGF-beta 1 stimulates thymidine incorporation and the growth rate of mouse NIH3T3 fibroblasts and of those cells transformed by the EJ-H-ras oncogene (TR15 cells), in the presence and the absence of serum. Thymidine incorporation, in serum-deprived cells, is stimulated to a higher degree by 0.1-1 ng/ml of TGF-beta in NIH3T3 than in TR15 cells, which have a 10-fold higher basal level of incorporation. In both cell types TGF-beta 1 is as active, or more active than other mitogens (TGF-alpha, PDGF-AB, bFGF) at the same concentration. The growth rate of NIH3T3 cells, in low serum or serum-free (S-) medium, is stimulated by only 10 picograms/ml of TGF-beta 1, and that of TR15 cells, in S- medium, by only 1 picogram/ml. In contrast, TGF-beta 1 inhibits mitogenically unestablished mouse embryo fibroblasts and these fibroblasts immortalized spontaneously and able to grow in S- medium. It also inhibits the anchorage-independent growth of TR15 cells. NIH3T3 and TR15 cells respond, similarly, to TGF-beta activated by acification of their culture medium. The kinetics of thymidine incorporation and of activation of the c-myc proto-oncogene, observed already after 1 hr, in treated NIH3T3 and TR15 cells, suggests a direct mitogenic stimulation. The level of activated c-myc RNA is 2-fold higher at 2 hr, and subsequently decreases relatively less in the TR15 cells.
Benzakour
O
O
Unité 1443 CNRS, Institut Curie-Biologie, Orsay, France.
Merzak
A
A
Dooghe
Y
Y
Pironin
M
M
Lawrence
D
D
Vigier
P
P
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D011905:Genes, ras; D007700:Kinetics; D051379:Mice; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004247:DNA; D013936:Thymidine