title: Inhibition of 125I-epidermal growth factor binding to cultured keratinocytes by antiproliferative molecules gamma interferon, cyclosporin A, and transforming growth factor-beta.
abstract: The growth of cultured human keratinocytes (KC) is inhibited by gamma interferon (IFN-gamma), cyclosporin A and transforming growth factor-beta, but not by tumor necrosis factor. When these antiproliferative molecules were added to KC they induced a concentration and time-dependent inhibition of 125I-epidermal growth factor (I-EGF) binding. These anti-proliferative molecules primarily reduced the number of binding sites by approximately 25%-50% without affecting the binding affinity. Tumor necrosis factor did not influence the ligand binding by I-EGF. In parallel with the ability of the antiproliferative molecules to inhibit I-EGF binding, there was an increase in transforming growth factor-alpha production. These results suggest that several different antiproliferative molecules may share a common mechanism to inhibit cell growth by reducing I-EGF binding to KC.
authors.affiliation: Department of Pathology, University of Michigan Medical Center, Ann Arbor.
authors.forename: B J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: R S
authors.initials: RS
authors.lastname: Mitra
mesh_terms: D003524:Cyclosporins / Q000494:pharmacology*; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D015291:Transforming Growth Factors / Q000494:pharmacology*
chemical_list: D003524:Cyclosporins; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D007371:Interferon-gamma