MYC and E1A Oncogenes Alter the Response of PC12 Cells to Nerve Growth Factor and Block Differentiation: A Thesis
AuthorsSchiavi, Susan C.
Faculty AdvisorDr. Gary L. Johnson
Academic ProgramBiochemistry and Molecular Pharmacology
UMass Chan AffiliationsBiochemistry
Document TypeDoctoral Dissertation
KeywordsNerve Growth Factor
Proto-Oncogene Proteins c-myc
Adenovirus E1A Proteins
Amino Acids, Peptides, and Proteins
Animal Experimentation and Research
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AbstractPC12 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.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/31568
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