Molecular markers of IGF-I-mediated mitogenesis

Exp Cell Res. 1998 Jul 10;242(1):361-72. doi: 10.1006/excr.1998.4113.


The aim of these investigations was to identify a number of molecular markers that correlate to growth stimulation by IGF-I. For this purpose, we have selected four cell lines that respond equally well to growth stimulation by serum, but differ in their proliferative response to IGF-I. Two cell lines (R503 and R600 cells) respond to IGF-I with both DNA synthesis and cell division, a third cell line (R508 cells) can enter S phase after IGF-I, but the cells do not divide, and a fourth one (R12 cells) totally fails to respond to IGF-I with growth. Using these cell lines, all of which had an intact mitogenic response program to serum, we show that: (1) an increase in GTP/GDP ratio is an early event that distinguishes cells capable of entering S phase after IGF-I from cells that do not; (2) all cells that are induced to synthesize DNA by IGF-I have increased phosphorylation of MAP kinases, regardless of their ability to divide; (3) the same cell lines display a similar increase in cyclin A and B expression at early times after stimulation; and (4) cyclin levels and cyclin B-associated cdc2 kinase activity remain elevated at later times only in cells that undergo cell division. These results establish certain parameters of IGF-I-mediated mitogenesis and clearly separate the occurrence of DNA synthesis from cell division in certain situations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis
  • Biomarkers / analysis*
  • Blood
  • CDC2 Protein Kinase / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Adhesion
  • Cell Division
  • Cell Line
  • Cyclin A / biosynthesis
  • Cyclin B / biosynthesis
  • DNA / biosynthesis
  • Guanosine Diphosphate / analysis
  • Guanosine Triphosphate / analysis
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mitogens / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins p21(ras) / analysis
  • RNA, Messenger / analysis
  • S Phase


  • Biomarkers
  • Cyclin A
  • Cyclin B
  • Mitogens
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Guanosine Diphosphate
  • Insulin-Like Growth Factor I
  • Guanosine Triphosphate
  • DNA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • CDC2 Protein Kinase
  • Proto-Oncogene Proteins p21(ras)