myc and E1A oncogenes alter the responses of PC12 cells to nerve growth factor and block differentiation.
PC12 rat pheochromocytoma cells respond to nerve growth factor (NGF) by neuronal differentiation and partial growth arrest. Mouse c-myc and adenovirus E1A genes were introduced into PC12 cells to study the influence of these nuclear oncogenes on neuronal differentiation. Expression of myc or E1A blocked morphological differentiation and caused NGF to stimulate rather than inhibit cell proliferation. NGF binding to cell surface receptors and ornithine decarboxylase induction were similar in myc- and E1A-expressing clones compared with wild-type PC12 cells, suggesting that changes in the cellular response to NGF were at a post-receptor level. These results illustrate that NGF can promote either growth or differentiation of PC12 cells, and that myc or E1A alter the phenotypic responses to growth factors and hormones.
Maruyama
K
K
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Schiavi
S C
SC
Huse
W
W
Johnson
G L
GL
Ruley
H E
HE
D017456:Adenovirus Early Proteins; D002454:Cell Differentiation; D002455:Cell Division; D004261:DNA Replication / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D009414:Nerve Growth Factors / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D009857:Oncogenes; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010673:Pheochromocytoma; D011956:Receptors, Cell Surface / Q000502:physiology; D017475:Receptors, Nerve Growth Factor; D014407:Tumor Cells, Cultured
D017456:Adenovirus Early Proteins; D009414:Nerve Growth Factors; D009856:Oncogene Proteins, Viral; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D009955:Ornithine Decarboxylase