ROLE OF ONCOGENES IN ERYTHROID DIFFERENTIATION

The identification of cellular oncogenes has allowed us the opportunity to define the malignant process and cellular differentiation within the context of a relatively small subset of genes. We have been studying the role of the c-myc oncogene in the differentiation of mouse erythroleukemia (MEL) cells. The major goal of this proposal is to study the mechanisms by which the c-myc regulation we have observed results in the terminal erythroid differentiation of MEL cells. Our approach will be to transfect MEL cells with c-myc clones attached to the mouse metallotionein I promoter and to study the effects of independently regulated c-myc on MEL cell differentiation. We also will determine whether the changes we have observed in c-myc mRNA levels during MEL cell differentiation are due to transcriptional or post-transcriptional controls. If control is exerted on the transcriptional level, we will be able to plan future experiments to determine the DNA sequences responsible for the rapid c-myc mRNA changes we have observed in MEL cells. Another aspect of MEL cell differentiation we will investigate is the relationship between DNA synthesis and cellular differentiation. We will relate these parameter to c-myc regulation in an attempt to clarify a controversy regarding the necessity for DNA synthesis in MEL cell differentiation. Finally, we will study the role of other cellular oncogenes in the MEL cell differentiation process. Eventually, we hope to perform MEL cell transfections using other oncogenes in order to demonstrate relationships between c-myc regulation, the expression of other cellular oncogenes, and MEL cell differentiation. The purpose of these experiments is to further understand the link between transformed and differentiated states in terms of the regulation of cellular oncogenes. (X)