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 biological activity the gene product p21 ras needs to be bound to the cell membrane by a farnesyl residue. Treatment of tumor cells with lovastatin reduces the availability of farnesyl pyrophosphate for the modification of the ras proteins. The membrane localization of p21 ras has been reduced by 30-36% after the tumor cells have grown in the presence of 10 microM lovastatin for 7 days. The extent of the inhibition depends on the growth kinetics of the cell lines.
Girgert
R
R
Department of Pediatric Surgery, University of Tübingen, FRG.
Marini
P
P
Janessa
A
A
Bruchelt
G
G
Treuner
J
J
Schweizer
P
P
D000208:Acute Disease; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology*; D009154:Mutation; D009447:Neuroblastoma / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008148:Lovastatin; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)