Role of c-kit receptor tyrosine kinase in the development, survival and neoplastic transformation of mast cells

Pathol Int. 1996 Dec;46(12):933-8. doi: 10.1111/j.1440-1827.1996.tb03571.x.

Abstract

The c-kit gene is allelic with the dominant spotting (W) locus on mouse chromosome 5 and encodes a receptor tyrosine kinase. The ligand for c-kit receptor is stem cell factor (SCF), which is the principal growth factor for mast cells. The loss-of-function mutations of c-kit receptor affect the development of mast cells, thereby resulting in a depletion of mast cells. The abundant expression of c-kit receptor is indispensable for the survival of mast cells. In addition, the gain-of-function mutations of c-kit receptor were found in several tumor mast cell lines. When these gain-of-function mutations were introduced to cells of murine interleukin (IL)-3-dependent cell lines, the expression of c-kit receptor with constitutive tyrosine kinase activity not only abrogated the IL-3 requirement of the cells, but also caused them to become tumorigenic in nude athymic mice. The gain-of-function mutations of c-kit receptor appear to result in the malignant transformation of mast cells. Taken together, the signals from the c-kit receptor are essential for the development, survival, and malignant transformation of mast cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Survival / physiology
  • Cell Transformation, Neoplastic*
  • Humans
  • Mast Cells / pathology
  • Mast Cells / physiology*
  • Mice
  • Mice, Nude
  • Mutation
  • Proto-Oncogene Proteins c-kit / genetics*
  • Rats
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Stem Cell Factor / genetics

Substances

  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases