c-Myc and cancer metabolism

Abstract

The processes of cellular growth regulation and cellular metabolism are closely interrelated. The c-Myc oncogene is a "master regulator" which controls many aspects of both of these processes. The metabolic changes which occur in transformed cells, many of which are driven by c-Myc overexpression, are necessary to support the increased need for nucleic acids, proteins, and lipids necessary for rapid cellular proliferation. At the same time, c-Myc overexpression results in coordinated changes in level of expression of gene families which result in increased cellular proliferation. This interesting duality of c-Myc effects places it in the mainstream of transformational changes and gives it a very important role in regulating the "transformed phenotype." The effects induced by c-Myc can occur either as a "primary oncogene" which is activated by amplification or translocation or as a downstream effect of other activated oncogenes. In either case, it appears that c-Myc plays a central role in sustaining the changes which occur with transformation. Although efforts to use c-Myc as a therapeutic target have been quite frustrating, it appears that this may change in the next few years.

Figure 1

Diagram of Myc effects in transformed cells. There are a wide variety of downstream pathways which are both positively and negatively regulated by Myc expression.

Figure 2

Pleiotropic Effects of c-Myc Expression. The c-myc gene has a variety of molecular and cellular effects (which are closely related). These effects result from myc-mediated changes in large gene families which drive cellular functions. Microarray studies have shown that these changes occur in concert and have major effects on cellular function.