Regulation of BALB/c 3T3 fibroblast proliferation by B-myb is accompanied by selective activation of cdc2 and cyclin D1 expression

Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10415-9. doi: 10.1073/pnas.89.21.10415.

Abstract

The B-myb gene is expressed in many cell types at the G1/S transition of the cell cycle. Inhibition of B-myb expression in BALB/c 3T3 fibroblasts by introduction of a B-myb antisense construct greatly diminished cell proliferation, whereas constitutive expression of a human B-myb cDNA in these cells reduced their growth factor requirements and induced a transformed phenotype. Constitutive expression of B-myb cDNA was accompanied by activation of cyclin D1 and cdc2 expression but not of cyclin A and cyclin B. Transfection of BALB/B-myb cells (a cell line expressing high levels of exogenous human B-myb) with a cyclin D1 antisense construct drastically reduced cloning efficiency of these cells. These results suggest that the B-myb-encoded product regulates fibroblast proliferation by activating cdc2 and cyclin D1 gene expression and that abnormal expression of cyclin D1 might be a step in the process of transformation.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • CDC2 Protein Kinase / biosynthesis*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / isolation & purification
  • Cell Division*
  • Cloning, Molecular
  • Cyclins / biosynthesis*
  • Cyclins / genetics
  • Cyclins / isolation & purification
  • DNA, Neoplasm / genetics
  • Gene Expression
  • Humans
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • Oncogene Proteins v-myb
  • Oncogenes*
  • Polymerase Chain Reaction / methods
  • Protein-Tyrosine Kinases / genetics*
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • Retroviridae Proteins, Oncogenic / genetics*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cyclins
  • DNA, Neoplasm
  • Oligodeoxyribonucleotides
  • Oligonucleotides, Antisense
  • Oncogene Proteins v-myb
  • RNA, Messenger
  • Retroviridae Proteins, Oncogenic
  • Protein-Tyrosine Kinases
  • CDC2 Protein Kinase