TGF-beta inhibition of endothelial cell proliferation: alteration of EGF binding and EGF-induced growth-regulatory (competence) gene expression.
Transforming growth factor-beta (TGF-beta) inhibits the growth of endothelial cells derived from various sources, including human umbilical vein, bovine aorta, and rat heart. Long-term exposure of rat heart endothelial cells to TGF-beta also induces dramatic changes in morphology that are characteristic of senescent cells. These changes are accompanied by a decrease in the number of high-affinity receptors for epidermal growth factor (EGF), with almost no change in total receptor number. Additionally, the EGF-induced expression of specific competence genes (c-myc, JE, KC) is decreased, whereas the induction of c-fos gene expression by EGF is unaltered by TGF-beta treatment. These data suggest that growth inhibitors such as TGF-beta may act by altering the cell's response to growth-stimulatory factors.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010455:Peptides / Q000494:pharmacology*; D011519:Proto-Oncogenes / Q000187:drug effects*; D015291:Transforming Growth Factors
D006133:Growth Substances; D010455:Peptides; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D066246:ErbB Receptors