Permissivity for methotrexate-induced DHFR gene amplification correlates with the metastatic potential of rat adenocarcinoma cells

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-metastat...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1994-04, Vol.15 (4), p.695-700
Main Author: LÜCKE-HUHLE, C
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - pathology
Animals
Biological and medical sciences
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
DNA, Neoplasm - genetics
Drug Resistance
Fundamental and applied biological sciences. Psychology
Gene Amplification - drug effects
Genes, myc
Genes, p53
Genes, ras
Methotrexate - pharmacology
Molecular and cellular biology
Neoplasm Metastasis
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-raf
Rats
Tetrahydrofolate Dehydrogenase - genetics
Tumor Cells, Cultured
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Summary: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 seen to confer tumorgenicity but not permissivity for gene amplification.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/15.4.695