INHIBITION OF THE MEMBRANE LOCALIZATION OF P21 RAS PROTEINS BY LOVASTATIN IN TUMOR-CELLS POSSESSING A MUTATED N-RAS GENE

Mutated ras genes are found in a variety of human tumors. For biologic al activity the gene product p21 ras needs to be bound to the cell mem brane by a farnesyl residue. Treatment of tumor cells with lovastatin reduces the availability of farnesyl pyrophosphate for the modificatio n of the ras proteins. The membrane localization of p21 ras has been r educed by 30-36% after the tumor cells have grown in the presence of 1 0 mu M lovastatin for 7 days. The extent of the inhibition depends on the growth kinetics of the cell lines.