Cellular differentiation is a complex process for which the molecular mechanisms are poorly understood. Differentiation is frequently associated with an altered pattern of growth. One extreme example of the coupling of growth and differentiation is terminal differentiation, whereby cells irreversibly lose proliferative capacity in addition to expressing new structural genes. How changes in growth potential are related to expression of the differentiated phenotype is at present unknown. In general, malignant cells which have lost growth control appear """"""""frozen"""""""" in a particular state of differentiation. Some transformed cells can be induced to terminally differentiate in culture (and others fail to differentiate in response to appropriate signals). We have focussed our attention on questions related to the role of oncogenes in the differentiation process of murine erythroleukemia (MEL) cells. In our initial studies, we were able to demonstrate that overexpression of the c- myc family of oncogenes blocks inducer mediated differentiation of MEL cells. Based on reports which demonstrate specific interactions between Myc and Max resulting in a transcriptionally active complex and the recent discovery of two additional gene products Mad and Mxi1 which are thought to be involved in regulating the formation of Myc/Max heterodimers. We investigated the expression, regulation, and role of the max gene in growth and differentiation of MEL cells. In addition, we cloned the Mad and Mxi1 genes. Their functions and expression in MEL cells are currently being investigated.
