Granulocyte-macrophage colony-stimulating factor abrogates transforming growth factor-beta 1-mediated cell cycle arrest by up-regulating cyclin D2/Cdk6

Br J Haematol. 1997 Sep;98(3):520-7. doi: 10.1046/j.1365-2141.1997.2643079.x.


The role of positive and negative cytokine interactions in G1 cell cycle regulation of haemopoietic cells was analysed by determination of the expression patterns of D-type cyclins and cyclin-dependent kinases (cdks) in SKM-1 myelodysplastic syndrome (MDS) cells incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or transforming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 inhibited SKM-1 cell proliferation due to the cell cycle arrest in G1 phase. GM-CSF abrogated the TGF-beta 1-mediated G1 arrest in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 1-mediated G1 arrest correlated with the down-regulation of cdk4, cdk6 and cyclin D2, and that abrogation of TGF-beta 1-mediated G1 arrest by GM-CSF correlated with the constitutive over-expression of cyclin D2 and cdk6 but not cdk4. These results suggest the importance of cyclin D2/cdk6 levels in abrogating G1 arrest in cells exposed to TGF-beta 1, and raise the possibility that the GM-CSF-mediated up-regulatory pathway of signal transduction through cyclin D2/cdk6 differs from the TGF-beta 1-cdk4-mediated pathway in SKM-1 cells. This signal transduction pathway through cyclin D2/cdk6 might play an important role in haemopoietic regulation by the cytokine network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cyclin D1 / metabolism
  • Cyclin D2
  • Cyclin D3
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinases*
  • Cyclins / metabolism
  • Drug Interactions
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Myelodysplastic Syndromes / pathology
  • Protein Serine-Threonine Kinases / metabolism*
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured
  • Up-Regulation


  • CCND2 protein, human
  • CCND3 protein, human
  • Cyclin D2
  • Cyclin D3
  • Cyclins
  • Transforming Growth Factor beta
  • Cyclin D1
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Protein Serine-Threonine Kinases
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6
  • Cyclin-Dependent Kinases