Inhibition of proliferation of human melanocytes by a KIT antisense oligodeoxynucleotide: implications for human piebaldism and mouse dominant white spotting (W).
KIT constitutes the cell surface transmembrane receptor protein tyrosine kinase for a growth factor variously termed steel factor (SLF), stem cell factor, mast cell growth factor, or Kit ligand. Inherited mutations of the KIT gene result in piebaldism in humans and dominant white spotting (W) in mice. Patches of hypopigmented skin and hair in these disorders represent regions lacking in melanocytes, the result of defective melanoblast differentiation, migration, proliferation, or survival during embryonic development. Here we show that incubation of normal human melanocytes with a KIT antisense oligodeoxynucleotide greatly inhibits cell proliferation in culture, whereas incubation with a KIT sense oligodeoxynucleotide has no effect. The KIT oligodeoxynucleotides also had little or no effect on cell survival.
Spritz
R A
RA
Department of Medical Genetics, University of Wisconsin, Madison.
Ho
L
L
Strunk
K M
KM
D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics*; D006801:Humans; D008544:Melanocytes / Q000166:cytology*; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016116:Piebaldism / Q000235:genetics; D019089:Stem Cell Factor
D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D016376:Oligonucleotides, Antisense; D019089:Stem Cell Factor