Progression of human cutaneous melanoma is associated with loss of expression of c-kit proto-oncogene receptor.
Mutations at the white spotting (w) locus in mice have deleterious effects on germ cells, melanocytes and hematopoietic stem cells. The w locus encodes the c-kit tyrosine-kinase receptor whose ligand is the product of the SI locus. Using monoclonal antibodies (MAb(s)) to the extracellular domain, we have evaluated the expression of c-kit in normal and transformed melanocytes. This cell lineage synthesizes a receptor with a mw of 145 kDa. The gene product is expressed in epidermal melanocytes and in a fraction of nevocytic and blue nevi. In primary melanomas, loss of the receptor is observed in more invasive lesions. Only 30% of the metastatic lesions express detectable levels of the receptor. These findings demonstrate that the c-kit product is down-regulated in melanocytes following malignant transformation. The functional relevance of this modulation remains to be evaluated.
Natali
P G
PG
Regina Elena Cancer Institute, Rome, Italy.
Nicotra
M R
MR
Winkler
A B
AB
Cavaliere
R
R
Bigotti
A
A
Ullrich
A
A
D000911:Antibodies, Monoclonal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008544:Melanocytes / Q000737:chemistry*; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology / Q000556:secondary; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019009:Proto-Oncogene Proteins c-kit; D011956:Receptors, Cell Surface / Q000032:analysis*; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology
D000911:Antibodies, Monoclonal; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D019009:Proto-Oncogene Proteins c-kit