Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas

Neoplasia. 2011 Mar;13(3):276-85. doi: 10.1593/neo.101540.

Abstract

Bone morphogenetic protein 7 (BMP-7) belongs to the superfamily of transforming growth factor β-like cytokines, which can act either as tumor suppressors or as tumor promoters depending on cell type and differentiation. Our investigations focused on analyzing the effects of BMP-7 during glioma cell proliferation in vitro and in vivo. BMP-7 treatment decreased the proliferation of Gli36ΔEGFR-LITG glioma cells up to 50%through a cell cycle arrest in the G(1) phase but not by induction of apoptosis. This effect was mediated by the modulation of the expression and phosphorylation of cyclin-dependent kinase 2, cyclin-dependent kinase inhibitor p21, and downstream retinoblastoma protein. Furthermore, in vivo optical imaging of luciferase activity of Gli36ΔEGFR-LITG cells implanted intracranially into nude mice in the presence or absence of BMP-7 treatment corroborated the antiproliferative effects of this cytokine. This report clearly underlines the tumor-suppressive role of BMP-7 in glioma-derived cells. Taken together, our results indicate that manipulating the BMP/transforming growth factor β signaling cascade may serve as a new strategy for imaging-guided molecular-targeted therapy of malignant gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism*
  • Cell Differentiation
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Fluorescent Antibody Technique
  • G1 Phase*
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology*
  • Luciferases / metabolism
  • Luminescence
  • Mice
  • Mice, Inbred BALB C
  • Molecular Targeted Therapy
  • Phosphorylation
  • RNA, Messenger / genetics
  • Retinoblastoma Protein / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / metabolism

Substances

  • Bone Morphogenetic Protein 7
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger
  • Retinoblastoma Protein
  • Transforming Growth Factor beta
  • Luciferases
  • Cyclin-Dependent Kinase 2