Nerve growth factor (NGF) induces neuronal differentiation in neuroblastoma cells transfected with the NGF receptor cDNA.
Human nerve growth factor (NGF) receptor (NGFR) cDNA was transfected into a neuroblastoma cell line (HTLA 230) which does not express a functional NGF-NGFR signal transduction cascade. Short-term treatment of stably transfected cells (98-3) expressing membrane-bound NGF receptor molecules resulted in a cell cycle-dependent, transient expression of the c-fos gene upon treatment with NGF, suggesting the presence of functional high-affinity NGFR. Extensive outgrowth of neurites and cessation of DNA synthesis occurred in transfectants grown on an extracellular matrix after long-term treatment with NGF, suggesting terminal differentiation. Our data support the idea that introduction of a constitutively expressed NGFR cDNA into cells with neuronal background results in the assembly of a functional NGF-NGFR signal cascade in a permissive extracellular environment.
Matsushima
H
H
Department of Pathology, Children's Hospital of Los Angeles, California 90027.
Bogenmann
E
E
D000818:Animals; D001345:Autoradiography; D002454:Cell Differentiation; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D004273:DNA, Neoplasm; D009414:Nerve Growth Factors; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D014316:Tritium; D013936:Thymidine