Late signals are required for the stimulation of DNA synthesis in rat mammary fibroblasts by growth factors

Biosci Rep. 1996 Jun;16(3):249-63. doi: 10.1007/BF01207339.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cell Line
  • Clone Cells
  • DNA / biosynthesis*
  • Dose-Response Relationship, Drug
  • Epidermal Growth Factor / pharmacology
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Growth Substances / pharmacology*
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / physiology*
  • Rats
  • Signal Transduction / physiology*
  • Time Factors

Substances

  • Growth Substances
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor
  • DNA