STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity

Oncogene. 2001 Jul 27;20(33):4528-36. doi: 10.1038/sj.onc.1204590.


Activating mutations of c-kit at codon 816 (Asp(816)) have been identified in variety of malignancies, including acute myeloid leukemia (AML), mastocytosis and germ cell tumors. The mutant c-Kit receptor confers cytokine independence and induces tumorigenicity. However, the molecular mechanisms, particularly the changes in the signal transduction pathways, responsible for these biological effects induced by mutant c-Kit are largely undefined. Using the human embryonic kidney cell line, 293, we show in the current report that constitutive activation of STAT3 and STAT1 is associated with D816H mutant c-Kit. Transfection of dominant negative STAT3, but not STAT1 inhibits mutant c-Kit mediated anchorage-independent growth in vitro and tumor formation in vivo. Expression of constitutively activated STAT3 restores the mutant c-Kit receptor's transforming ability in 293 cells. These results demonstrate that activation of STAT3 by Asp(816) mutant c-Kit is required for the anchorage-independent growth and tumorigenicity induced by Asp(816) mutant c-Kit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Cell Division / drug effects
  • Cell Line, Transformed / drug effects
  • Cell Line, Transformed / transplantation
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • Codon / genetics
  • DNA-Binding Proteins / physiology*
  • Dimerization
  • Humans
  • Kidney / cytology
  • Kidney / embryology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mutation, Missense
  • Neoplasm Transplantation
  • Oncogenes*
  • Proto-Oncogene Proteins c-kit / chemistry
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / physiology*
  • Recombinant Proteins / pharmacology
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction
  • Stem Cell Factor / pharmacology
  • Trans-Activators / physiology*
  • Transfection


  • Codon
  • DNA-Binding Proteins
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Stem Cell Factor
  • Trans-Activators
  • Proto-Oncogene Proteins c-kit