Induction of c-sis mRNA and activity similar to platelet-derived growth factor by transforming growth factor beta: a proposed model for indirect mitogenesis involving autocrine activity.
Treatment of quiescent cultures of mouse embryo-derived AKR-2B cells with transforming growth factor beta resulted in an early induction of c-sis mRNA. The increase in c-sis mRNA was followed by a corresponding increase in protein similar to platelet-derived growth factor (PDGF) in the culture medium. In addition, PDGF-regulated genes (c-fos and c-myc) were stimulated by transforming growth factor beta with delayed kinetics relative to that seen in other cell systems with direct PDGF stimulation. A model is proposed in which the monolayer mitogenicity of transforming growth factor beta is mediated by the induction of c-sis and PDGF and the subsequent autocrine stimulation of c-fos, c-myc, and other PDGF-inducible genes.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008938:Mitosis / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011519:Proto-Oncogenes; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D014158:Transcription, Genetic / Q000187:drug effects; D015291:Transforming Growth Factors
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D015291:Transforming Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor