CD-117 mini-review (kinda long)

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From:Abizar Lakdawalla <>
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c-kit (CD117) is a transmembrane tyrosine kinase receptor and proto-oncogene
protein present on cells of hematopoietic lineage.  Structur-ally, the c-kit
protein contains an immunoglobulin-like extracellular domain, and a tyrosine
kinase domain with a hydrophilic insert.  The ligand for c-kit is known as
stem cell factor (SCF), mast cell growth factor, kit ligand (KL) or steel
factor. Binding of c-kit to stem cell factor is required for the
proliferation or differentiation of hematopoietic cell lines in culture.
Leukemias derived from erythroid, megakaryocytic or mast cell lineage
express the c-kit ligand, while leukemias of lymphoid lineage (ALL) do not.
c-kit has also been shown to be critical in game-togenesis, development of
melanocytes and, possibly, the development of the central nervous system.

c-kit is markedly expressed on all mast cells whether cultured from
pe-ripheral blood or detected in normal adult skin.  It is also positive in
normal melanocytes. Several studies have characterized c-kit expression in a
large sampling of normal human tissues. These studies showed c-kit
expression in tissue mast cells, skin basal cells, melanocytes, breast
glandular epithelial cells, glandular epithelial cells from parotid, dermal
sweat gland, esophageal glands, testicular and ovarian interstitial cells.
c-kit was observed to be regionally distributed in the central nervous
system.  Abnormal expression of c-kit has been implicated in the
patho-genesis of myeloid leukemias.  c-kit expression has also been
demon-strated in solid tumors including melanoma, breast cancer, and small
cell lung cancer.  Normal breast ductal epithelial cells stain positive for
c-kit, and approximately 20% of breast carcinomas retain c-kit expres-sion
although the pattern of staining shifts from peripheral membrane staining to
diffuse cytoplasmic staining.  c-kit expression is reduced in the smooth
muscle cells in aganglionic bowel of Hirschsprung's disease, supporting the
hypothesis that c-kit is necessary for embryonic differ-entiation of the
bowel.  c-kit expression is high in cells surrounding the myenteric plexus
that are absent in the aganglionic specimens. c-kit expression is found in
the seminoma subtype of testicular germ cell tumors, but is absent in
non-seminoma subtypes. Expressed in all cells of hematopoietic lineage.

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