Effect of polyamine depletion on c-myc expression in human colon carcinoma cells

Polyamine depletion generally results in an inhibition of cell growth. However, the precise role of polyamines in the regulation of cell proliferation is unknown. In the present study, we demonstrate that polyamine depletion induced by 2-difluoromethylornithine in COLO 320 human colon carcinoma cells results in a greater than 90% decrease in expression of a key gene in the maintenance of cell growth, the c-myc protooncogene. The decrease in c-myc expression accompanying polyamine depletion appears to occur at the transcriptional level. It is not simply a result of decreased growth rate since growth-inhibited cells at confluence maintain a high level of c-myc expression. It is also not due to a change in cell cycle phase distribution and is not a reflection of a generalized decrease in gene expression which accompanies a decrease in cellular proliferation. Thus, the expression of the histone H2A gene was similar to and temporally paralleled the growth status of both treated and untreated cells, while the β-actin and ornithine decarboxylase genes actually had increased expression during polyamine depletion. These studies demonstrate that polyamines may be critical to the expression of c-myc and suggest one mechanism by which they modulate cell growth.