MYC and E1A Oncogenes Alter the Response of PC12 Cells to Nerve Growth Factor and Block Differentiation: A Thesis
Authors
Schiavi, Susan C.Faculty Advisor
Dr. Gary L. JohnsonAcademic Program
Biochemistry and Molecular PharmacologyUMass Chan Affiliations
BiochemistryDocument Type
Doctoral DissertationPublication Date
1988-08-01Keywords
Nerve Growth FactorProto-Oncogene Proteins c-myc
Adenovirus E1A Proteins
PC12 Cells
Cell Differentiation
Neurons
Transcription Factors
Mice
Amino Acids, Peptides, and Proteins
Animal Experimentation and Research
Cells
Genetic Phenomena
Nervous System
Viruses
Metadata
Show full item recordAbstract
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 and E1A blocked morphological differentiation and caused NGF to stimulate rather than inhibit cell proliferation. NGF binding to cell surface receptors, activation of ribosomal S6 kinase, 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. The ability of myc and E1A expression to block the transcription-dependent induction of microtubule associated proteins by NGF further suggested that these genes may inhibit differentiation by interfering with NGP's ability to regulate transcription. 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.DOI
10.13028/3hcw-dw22Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31568Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/3hcw-dw22