title: Permissivity for methotrexate-induced DHFR gene amplification correlates with the metastatic potential of rat adenocarcinoma cells.
abstract: During selection for methotrexate (MTX) resistance the metastatic subclone BSp73ASML of a spontaneous rat adenocarcinoma and a metastatic transfectant containing the metastogene META-1 underwent amplification of the dihydrofolate reductase (DHFR) gene at accelerated rates in contrast to non-metastatic but closely related BSp73AS cells. A four log increase in MTX resistance was associated with a 16-fold amplification and increased expression of the DHFR gene. The capacity for gene amplification in metastatic BSp73ASML cells was correlated with a deletion in the p53 gene and enhanced expression of the oncogene c-myc due to a 10-fold amplification of the myc gene. Increased expression of Ki-ras and c-raf in the non-metastatic BSp73AS cells seems to confer tumorigenicity but not permissivity for gene amplification.
authors.affiliation: Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Lücke-Huhle
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance; D005784:Gene Amplification / Q000187:drug effects; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D008727:Methotrexate / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D011518:Proto-Oncogene Proteins; D013762:Tetrahydrofolate Dehydrogenase; D019908:Proto-Oncogene Proteins c-raf; D008727:Methotrexate