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

Oncogene. 1992 Nov;7(11):2303-13.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Cell Communication
  • Cell Differentiation
  • Cell Division
  • Gene Expression
  • Humans
  • Melanocytes / cytology*
  • Melanoma / pathology*
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology
  • RNA, Messenger / analysis
  • Receptors, Fibroblast Growth Factor / analysis
  • Receptors, Fibroblast Growth Factor / genetics*

Substances

  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor