Role of c-kit receptor tyrosine kinase in the development, survival and neoplastic transformation of mast cells.
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.
Tsujimura
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Department of Pathology, Osaka University Medical School, Suita, Japan.
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D006801:Humans; D008407:Mast Cells / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D019089:Stem Cell Factor / Q000235:genetics
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases