EGF is incomplete mitogen in porcine aortic smooth muscle cells: DNA synthesis without cell division

S. P. Bagby, M. M. O'Reilly, E. A. Kirk, L. H. Mitchell, P. E. Stenberg, M. T. Makler, A. C. Bakke

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


To characterize growth effects of epidermal growth factor (EGF) in subconfluent quiescent porcine aortic vascular smooth muscle cells (VSMC), we measured DNA and protein synthesis by [3H]thymidine (Thd) and [35S]methionine (Met) incorporation, respectively, and cell proliferation rates over 0-6 days in Dulbecco's modified Eagle's-Ham's F-12 media containing 0.4% fetal calf serum (FCS) and insulin. EGF induced dose- dependent [3H]Thd uptake (P < 0.001); after 10-9 M EGF, DNA synthesis rate peaked at 24 h, averaging 77% of the response to 10% FCS, and then declined steeply with nadir at 48-60 h. Unexpectedly, EGF failed to induce cell proliferation in the first 4 days, leaving this initial burst of DNA synthesis (12-60 h) uncoupled from cell division. A second lesser but sustained phase of increased DNA synthesis, apparent by day 3-4, was associated with a small increase in cell number on day 6 (P < 0.05). The early unsustained burst of DNA synthesis reflects EGF's potent mitogenic efficacy for DNA synthesis (G1- to S-phase traversal), probably acting on a subset of cells partially synchronized initially at an EGF-responsive G0/G1 locus; the minimal cell division despite brisk DNA synthesis documents EGF's limited efficacy for (or inhibition of) late cell-cycle events required for completion of mitosis. Late cell-cycle processes are thus rate limiting. EGF also increased protein synthetic rate over control (P < 0.03) but to a lesser degree (P < 0.01) than 10% FCS. Indomethacin (10-6 M) did not alter DNA or proliferative responses to 10-9 M EGF but transiently augmented EGF-induced protein synthesis (P < 0.025) at 24 h only. We conclude that, in porcine aortic VSMC studied in 0.4% FCS-insulin, EGF is a potent mitogen for DNA synthesis but an incomplete mitogen for the late cell-cycle events required for completion of cell division, a pattern potentially relevant to the phenomenon of polyploidy observed in VSMC hypertrophy in vivo.

Original languageEnglish (US)
Pages (from-to)C578-C588
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3 31-3
StatePublished - Jan 1 1992
Externally publishedYes


  • [H]thymidine incorporation
  • [S]methionine incorporation
  • cell-cycle analysis
  • epidermal growth factor
  • indomethacin
  • medial hypertrophy
  • phenotype
  • polyploidy
  • proliferation
  • prostaglandins
  • protein synthesis
  • ultrastructure

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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