title: Late signals are required for the stimulation of DNA synthesis in rat mammary fibroblasts by growth factors.
abstract: Maximal stimulation of DNA synthesis in quiescent rat mammary (Rama) 27 fibroblasts is elicited by epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) 18 h after the initial addition of the growth factors-the 'lag' period. At maximally-stimulating concentrations, EGF and bFGF are interchangeable 9 h after their initial addition. When the initial concentration of growth factor is below that required to elicit a maximal response, it is possible to increase the level of DNA synthesis by increasing the concentration of growth factor 9 h after its initial addition. When the initial concentration of growth factor is high, substitution by a lower concentration of growth factor after 9 h allows a greater proportion of cells to synthesize DNA than would be expected from a continuous low dose of growth factor. Similar results are obtained when both the growth factor and its concentration are changed 9 h after the initial addition of growth factor. However, when EGF at a low concentration is substituted for a high concentration of EGF or bFGF the resulting increase in the levels of DNA synthesis is greater when EGF rather than bFGF is added for a second time. The half-life of the growth-stimulatory signals delivered by EGF and by bFGF 9 h after their initial addition is 1-2 h. These results suggest that to stimulate DNA synthesis: (i) EGF or bFGF must deliver a signal(s) continuously; (ii) the initial signals produced by EGF and bFGF are equivalent; (iii) the signals produced between 9-18 h by EGF may be different to those produced by bFGF.
authors.affiliation: Department of Biochemistry, University of Liverpool, UK.
authors.forename: H L
authors.initials: HL
authors.lastname: Chen
authors.forename: P S
authors.initials: PS
authors.lastname: Rudland
authors.forename: J A
authors.initials: JA
authors.lastname: Smith
authors.forename: D G
authors.initials: DG
authors.lastname: Fernig
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
chemical_list: D006133:Growth Substances; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D004247:DNA