GSBS Dissertations and Theses

Approval Date

August 1988

Document Type

Doctoral Dissertation

Department

Graduate School of Biomedical Sciences, Biochemistry

Subjects

Nerve Growth Factor; Proto-Oncogene Proteins c-myc; Adenovirus E1A Proteins; PC12 Cells; Cell Differentiation; Neurons; Transcription Factors; Mice; Academic Dissertations; Dissertations, UMMS

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 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.

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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