Current models of the molecular basis of malignant transformation propose that the pathogenesis of malignancy involves abnormal expression of cellular oncogenes. These genes, which are thought to be involved in the normal processes of growth and differentiation, have been found to have characteristic chromosomal changes in certain tumors which have been correlated with their altered expression.
The aim of this project is to investigate the regulation of the c- myc oncogene in both the normal process of differentiation and in the pathogenesis of malignancy. Burkitt lymphoma is a malignant lymphoma associated with characteristic chromosomal translocations between that oncogene and one of the three immunoglobulin gene loci. I propose to analyze the manner in which these somatic rearrangements affect the regulation of the c-myc gene in differentiating cells. HL60 and MEL cells are cell lines derived from hematopoietic malignancies. They can be induced to undergo phenotypic maturation upon exposure to DMSO in a process which is associated with a dramatic fall in the level of c-myc expression. I will study the regulation of an exogenous c-myc gene in these cells and examine its effect on the process of induction. I have transfected the c-myc gene, in its normal and rearranged forms, into HL60 and MEL cells; I now propose to assay the effect of induction on the transcriptional activity of these exogenous genes and correlate the regulation of the introduced genes with the phenotype associated with induction.
