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.
D000818:Animals; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D000518:Eflornithine / Q000494:pharmacology; D011905:Genes, ras; D009857:Oncogenes; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection
D011073:Polyamines; D013096:Spermine; C052614:N(1), N(12)-diethylspermine; D000518:Eflornithine