Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation.
Fibroblast growth factor receptor (FGFR-1) is expressed as a single 3.5-kb mRNA transcript in normal human melanocytes and in malignant melanomas as determined upon Northern hybridization to a cDNA clone encoding the membrane-spanning form of the human FGFR-1. Polyclonal antisera directed against the chicken FGFR recognized a 145-kDa protein in primary and metastatic melanomas. Antisense oligodeoxynucleotides targeted against the translation start site and a splice donor-acceptor site of human FGFR-1, in addition to inhibiting the proliferation of normal human melanocytes and malignant melanomas, caused extensive dendrite formation and severe disruption of cell-cell contact--morphological changes that were not observed upon inhibition of the genes encoding basic fibroblast growth factor (bFGF) and retinoic acid-alpha receptor. Thus, unlike in the case of the ligand bFGF, expression of the FGFR-1 may represent a requisite to prevent human melanocytes and malignant melanomas from undergoing (terminal) differentiation.
Becker
D
D
Department of Medicine, University of Pittsburgh, Pennsylvania 15261.
Lee
P L
PL
Rodeck
U
U
Herlyn
M
M
D001483:Base Sequence; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D015870:Gene Expression; D006801:Humans; D008544:Melanocytes / Q000166:cytology*; D008545:Melanoma / Q000473:pathology*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor