Overexpression of insulin receptors in fibroblast and ovary cells induces a ligand-mediated transformed phenotype

Mol Endocrinol. 1991 Mar;5(3):452-9. doi: 10.1210/mend-5-3-452.


To investigate whether overexpression of the insulin receptor results in altered cell growth we used NIH 3T3 cells transfected with a bovine papilloma virus/insulin receptor cDNA construct (3T3/HIR). These cells expressed high numbers of insulin receptors (mean +/- sd, 631.0 +/- 16.7 ng receptors/10(6) cells). Insulin significantly stimulated the growth of 3T3/HIR cells maintained in serum-free medium. Moreover, in these cells, insulin induced marked phenotypic changes, including alterations in cell shape, loss of contact inhibition, and focal growth. In contrast to 3T3/HIR cells, insulin was without effect in either wild-type 3T3 cells (3T3/wt), 3T3 cells transfected with the neomycin resistance gene (3T3/NEO), or the bovine papilloma virus (3T3/BPV). To assess the presence of anchorage-independent growth, cells were seeded in soft agar and inspected for colony formation. 3T3/HIR cells showed absent or minimal colony growth in the absence of insulin. However, there was a dose-dependent insulin-stimulated increase in both colony size and number. Insulin-stimulated colony formation was specifically inhibited by an insulin antagonist, monoclonal antibody MA-10. In the presence of 100 nM insulin, about 3% of cells formed large colonies. Insulin neither stimulated growth nor induced colony formation in 3T3/wt cells or 3T3/NEO cells. Insulin also stimulated colony formation in CHO cells transfected with an insulin receptor cDNA construct. In conclusion, overexpression of normal insulin receptors induces a ligand-dependent transformed phenotype. This phenomenon may have clinical relevance by conferring a selective growth advantage to tumor cells with high numbers of insulin receptors.

Publication types

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

MeSH terms

  • Agar
  • Animals
  • Cell Line
  • DNA / metabolism
  • Drug Resistance / genetics
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / ultrastructure
  • Gene Expression
  • Insulin / pharmacology
  • Mice
  • Mice, Nude
  • Neomycin / pharmacology
  • Ovary / drug effects
  • Ovary / metabolism*
  • Ovary / ultrastructure
  • Papillomaviridae / genetics
  • Phenotype
  • Receptor, Insulin / genetics*
  • Transfection
  • Transformation, Genetic*


  • Insulin
  • Agar
  • DNA
  • Receptor, Insulin
  • Neomycin