Density-dependent inhibition of cell growth by transforming growth factor-beta 1 in normal human fibroblasts.
We report here that transforming growth factor-beta 1 (TGF-beta 1) inhibits platelet-derived growth factor (PDGF)-induced DNA synthesis in normal human fibroblasts in a cell density-dependent manner; no inhibition was seen in sparse cultures, approximately 50% inhibition in confluent cell cultures, and an almost total inhibition in dense cultures. The PDGF-inducible genes c-myc and c-fos were induced also by TGF-beta 1. Simultaneous addition of TGF-beta 1 and PDGF resulted in sustained, rather than transient, expression of c-fos mRNA; c-fos mRNA was detected as long as 24 hr after addition of PDGF and TFG-beta 1. TGF-beta 1 also induced mRNA for the A chain, but not the B chain, of PDGF. Conversely, PDGF induced TGF-beta 1 mRNA in sparse but not in dense cultures. These data indicate the existence of a complex interdependent regulation of PDGF and TGF-beta mRNA expression which is influenced by the cell density.
Paulsson
Y
Y
Department of Pathology, University Hospital, Uppsala, Sweden.
Beckmann
M P
MP
Westermark
B
B
Heldin
C H
CH
D015152:Blotting, Northern; D002452:Cell Count; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D008934:Mitogens / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000378:metabolism; D015291:Transforming Growth Factors / Q000235:genetics / Q000502:physiology*
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015291:Transforming Growth Factors