Modulation of polyamine biosynthesis and transport by oncogene transfection.

The effects of oncogene expression on phenomena related to polyamine metabolism were examined in Rat-1 cells stably transfected with EJ2-ras or N-myc oncogenes. In ras-transfected cells, ornithine decarboxylase activity was about 12-times higher than in either the parent or N-myc-transfected cell lines. By contrast, polyamine uptake was markedly increased in N-myc-transfected cells, as indicated by their enhanced sensitivity to the antiproliferative and enzyme regulatory effects of the polyamine analog, N1, N12-bis(ethyl)spermine (BESm), their intracellular accumulation of BESm and by their increased sensitivity to the growth inhibitory effects of methylglyoxalbis(guanylhydrazone)--another analog which utilizes the polyamine transport mechanism. These associations between N-myc and ras expression and critical aspects of polyamine metabolism suggest a possible role for the latter in facilitating the growth promoting properties of these oncogenes.