» Articles » PMID: 281704

Amplified Dihydrofolate Reductase Genes Are Localized to a Homogeneously Staining Region of a Single Chromosome in a Methotrexate-resistant Chinese Hamster Ovary Cell Line

Overview
Specialty Science
Date 1978 Nov 1
PMID 281704
Citations 121
Authors
Affiliations
Soon will be listed here.
Abstract

Methotrexate-resistant Chinese hamster ovary cells selected for high resistance by progressive increments of methotrexate in the culture medium have levels of dihydrofolate reductase (tetrahydrofolate dehydrogenase, 7,8-dihydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) 200 times that of sensitive cells and a corresponding increase in the number of copies of the dihydrofolate reductase gene. The resistant cells contain an expanded region on the second chromosome (homogeneously staining region) that is not present in sensitive cells. In situ hybridization of DNA complementary to dihydrofolate reductase mRNA shows that the dihydrofolate reductase genes are specifically localized to the homogeneously staining region of this chromosome in the resistant cells.

Citing Articles

Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

Meng X, Ma J, Liu Y, Li S, Wang X, Zhu J Br J Cancer. 2024; 130(11):1819-1827.

PMID: 38594370 PMC: 11130306. DOI: 10.1038/s41416-024-02664-0.


Contribution of PGAP3 co-amplified and co-overexpressed with ERBB2 at 17q12 involved poor prognosis in gastric cancer.

Wang D, Hao S, He H, Zhang J, You G, Wu X J Cell Mol Med. 2023; 27(16):2424-2436.

PMID: 37386793 PMC: 10424286. DOI: 10.1111/jcmm.17828.


Use of CRISPR-based screens to identify mechanisms of chemotherapy resistance.

Alyateem G, Wade H, Bickert A, Lipsey C, Mondal P, Smith M Cancer Gene Ther. 2023; 30(8):1043-1050.

PMID: 37029320 PMC: 10722205. DOI: 10.1038/s41417-023-00608-z.


Demystifying extrachromosomal DNA circles: Categories, biogenesis, and cancer therapeutics.

Wu M, Rai K Comput Struct Biotechnol J. 2022; 20:6011-6022.

PMID: 36382182 PMC: 9647416. DOI: 10.1016/j.csbj.2022.10.033.


Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges.

Song K, Minami J, Huang A, Dehkordi S, Lomeli S, Luebeck J Cancer Discov. 2021; 12(4):1046-1069.

PMID: 34930786 PMC: 9192483. DOI: 10.1158/2159-8290.CD-20-0936.


References
1.
HAM R . CLONAL GROWTH OF MAMMALIAN CELLS IN A CHEMICALLY DEFINED, SYNTHETIC MEDIUM. Proc Natl Acad Sci U S A. 1965; 53:288-93. PMC: 219509. DOI: 10.1073/pnas.53.2.288. View

2.
Anderson R, Roth J . Tandem genetic duplications in phage and bacteria. Annu Rev Microbiol. 1977; 31:473-505. DOI: 10.1146/annurev.mi.31.100177.002353. View

3.
Chang A, Nunberg J, Kaufman R, Erlich H, Schimke R, Cohen S . Phenotypic expression in E. coli of a DNA sequence coding for mouse dihydrofolate reductase. Nature. 1978; 275(5681):617-24. DOI: 10.1038/275617a0. View

4.
Schimke R, Alt F, Kellems R, Kaufman R, Bertino J . Amplification of dihydrofolate reductase genes in methotrexate-resistant cultured mouse cells. Cold Spring Harb Symp Quant Biol. 1978; 42 Pt 2:649-57. DOI: 10.1101/sqb.1978.042.01.067. View

5.
Kaufman R, Bertino J, Schimke R . Quantitation of dihydrofolate reductase in individual parental and methotrexate-resistant murine cells. Use of a fluorescence activated cell sorter. J Biol Chem. 1978; 253(16):5852-60. View