KIT overexpression induces proliferation in astrocytes in an imatinib-responsive manner and associates with proliferation index in gliomas

Int J Cancer. 2008 Aug 15;123(4):793-800. doi: 10.1002/ijc.23576.


Activating gene mutations, gene amplifications and overexpressed proteins may be useful as targets for novel therapies. Alterations at chromosome locus 4q12 are associated with gliomas and the region harbors the receptor tyrosine kinase gene KIT, which is frequently amplified in gliomas, and also overexpressed in a subset of gliomas. KIT and its ligand stem cell factor are widely expressed in embryonic and adult mouse brain, and they play a role in many signal transduction pathways involved in cellular proliferation, differentiation and cancer cell metastasis. However, the function of KIT in gliomagenesis or disease progression remains unresolved as well as its role in neural and brain tumor development. In this study, we utilized lentivirus-mediated gene transfer to deliver the KIT gene into mouse astrocytes. The growth properties of KIT overexpressing cells were analyzed using several in vitro functional assays. The effect of receptor tyrosine kinase inhibitor imatinib on astrocyte growth was also investigated. Our results indicate that overexpression of KIT in mouse astrocytes promotes cell proliferation, and the increased proliferation is partly inhibited by imatinib treatment. Furthermore, KIT overexpression induces phenotypic changes in the cells suggesting that KIT may play a role in astrocyte growth regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / physiology
  • Astrocytes / drug effects*
  • Astrocytes / enzymology*
  • Astrocytes / pathology
  • Benzamides
  • Cell Growth Processes
  • Enzyme Activation
  • Glioma / drug therapy
  • Glioma / enzymology*
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Imatinib Mesylate
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Neoplastic Stem Cells
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-kit / biosynthesis*
  • Proto-Oncogene Proteins c-kit / genetics
  • Pyrimidines / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transfection


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9