Insulin-like growth factor-I induces cyclin-D1 expression in MG63 human osteosarcoma cells in vitro

Mol Endocrinol. 1994 Apr;8(4):510-7. doi: 10.1210/mend.8.4.8052269.

Abstract

The insulin-like growth factors (IGFs) stimulate cell division by modulating events occurring during the prereplicative (G1) phase of the cell cycle, but identification of the critical events has proved difficult. Recent observations suggest that progression through the cell cycle is dependent on the activation of a group of serine-threonine-specific protein kinases whose activities are regulated by accessory proteins, termed cyclins. The identification of cyclin species expressed during G1 has led to the hypothesis that modulation of cyclin expression may be the critical event regulated by growth factors. The present studies were undertaken to determine whether the IGFs regulate the expression of specific G1 cyclins in MG63, a human cell line that is unusually responsive to IGF, and to characterize this effect. We found that in these cells IGF-I stimulates the cyclin-dependent kinases, and that stimulation is associated with an increase in cyclin-D1 mRNA and protein expression. The increase in cyclin-D1 occurs early in G1 and corresponds to the portion of the cell cycle in which IGF acts on these cells. The increase in cyclin-D1 mRNA is due at least in part to an increase in the rate of transcription initiation of the gene. The mRNA levels of cyclin-B1 (a G2 cyclin) and two cyclin-dependent kinases, cdc2 and cdk2, also increased in response to IGF, but at later times. These results are consistent with the hypothesis that IGF modulation of D-type cyclin expression plays a role in the regulation of cell replication.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Bone Neoplasms / pathology*
  • CDC2-CDC28 Kinases*
  • Cell Division / drug effects
  • Cyclin D1
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases*
  • Cyclins / biosynthesis*
  • Cyclins / genetics
  • DNA Replication / drug effects
  • DNA, Neoplasm / biosynthesis
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Interphase / drug effects
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Oncogene Proteins / biosynthesis*
  • Oncogene Proteins / genetics
  • Osteosarcoma / pathology*
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / immunology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Cyclins
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Oncogene Proteins
  • RNA, Messenger
  • Cyclin D1
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases