Related Experiment Videos
myc and E1A oncogenes alter the responses of PC12 cells to nerve growth factor and block differentiation
K Maruyama1, S C Schiavi, W Huse
1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Abstract:
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.
Insights
Nuclear oncogenes Myc and E1A block nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells. These oncogenes redirect NGF
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- PC12 rat pheochromocytoma cells differentiate and arrest growth upon nerve growth factor (NGF) stimulation.
- Understanding the molecular mechanisms regulating cell fate decisions in response to growth factors is crucial.
Purpose of the Study:
- To investigate the impact of nuclear oncogenes, mouse c-myc and adenovirus E1A, on NGF-mediated neuronal differentiation in PC12 cells.
- To determine if these oncogenes alter the cellular response to NGF at a pre- or post-receptor level.
Main Methods:
- Introduction of mouse c-myc and adenovirus E1A genes into PC12 cells.
- Assessment of morphological differentiation and cell proliferation in response to NGF.
- Analysis of NGF receptor binding and ornithine decarboxylase induction.
Main Results:
- Expression of c-myc or E1A inhibited NGF-induced morphological differentiation in PC12 cells.
- NGF stimulated cell proliferation in oncogene-expressing cells, contrasting with growth arrest in wild-type cells.
- NGF receptor binding and ornithine decarboxylase induction remained comparable, indicating post-receptor alterations.
Conclusions:
- Nuclear oncogenes c-myc and E1A can override NGF's differentiation-promoting signal, favoring proliferation.
- These oncogenes modify the intracellular signaling pathways downstream of the NGF receptor.
- The study highlights the plasticity of PC12 cell responses to growth factors and hormones, influenced by oncogene expression.