A Study of Chromosomal Changes Associated with Amplified Dihydrofolate Reductase Genes in Rat Hepatoma Cells and Their Dedifferentiated Variants

We have examined the karyological consequences of dihydrofolate reductase gene amplification in a series of six rat hepatoma cell lines, all derived from the same clone. Cells of three of these lines express a series of liver-specific functions whereas those of three others fail to express these fun...

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Bibliographic Details
Published in:The Journal of cell biology 1984-08, Vol.99 (2), p.497-502
Main Authors: Fougere-Deschatrette, Catherine, Schimke, Robert T., Weil, Dominique, Weiss, Mary C.
Format: Article
Language:English
Subjects:
Animal cells
Animals
Biological and medical sciences
Cell cultures. Hybridization. Fusion
Cell Differentiation
Cell Line
Cell lines
Cells
Chromosome Banding
Chromosomes
Chromosomes - physiology
Drug Resistance
Fundamental and applied biological sciences. Psychology
Gene Amplification
Genes
Genetic Variation
Hepatocellular carcinoma
Hepatocytes
Karyotype
Karyotyping
Liver Neoplasms, Experimental - enzymology
Liver Neoplasms, Experimental - physiopathology
Metaphase
Methotrexate - toxicity
Molecular and cellular biology
Nucleic Acid Hybridization
Rats
Somatic cells
Stem cells
Tetrahydrofolate Dehydrogenase - genetics
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Summary:We have examined the karyological consequences of dihydrofolate reductase gene amplification in a series of six rat hepatoma cell lines, all derived from the same clone. Cells of three of these lines express a series of liver-specific functions whereas those of three others fail to express these functions. Cells of each line have been subjected to stepwise selection for methotrexate resistance and, in most cases, resistance is associated with a 40-50-fold amplification of sequences hybridizing to a dihydrofolate reductase cDNA probe. In one line no modified chromosome is observed, whereas in two others the amplified genes are associated with an expanded chromosomal region. R-banding analysis of these karyotypes showed that few changes have occurred. These observations apply to two of the well-differentiated lines, and to a variant able to revert to the differentiated state. In contrast, in the two stably dedifferentiated hepatoma cell lines, amplified dihydrofolate reductase genes are found on large chromosomes of variable size, on ring chromosomes, and on chromosomes containing terminal, median, or multiple centromeres. We conclude that the nature of the chromosomal changes associated with dihydrofolate reductase gene amplification are the result of differences in cell lines rather than in the protocols employed for selection.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.99.2.497