Home LiteratureArticle Details
PMID: 6144041 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Co-amplification of double minute chromosomes, multiple drug resistance, and cell surface P-glycoprotein in DNA-mediated transformants of mouse cells.

Molecular and cellular biology ·Vol. 4 ·No. 3 ·1984-03-00 ·Pages 500-6

Robertson SM, Ling V, Stanners CP

Abstract

A genetic system comprised of mammalian cell mutants which demonstrate concomitant resistance to a number of unrelated drugs has been described previously. The resistance is due to reduced cell membrane permeability and is correlated with the presence of large amounts of a plasma membrane glycoprotein termed P-glycoprotein. This system could represent a model for multiple drug resistance which develops in cancer patients treated with chemotherapeutic drugs. We demonstrate here that the multiple drug resistance phenotype can be transferred to mouse cells with DNA from a drug-resistant mutant and then amplified quantitatively by culture in media containing increasing concentrations of drug. The amount of P-glycoprotein was correlated directly with the degree of drug resistance in the transformants and amplified transformants. In addition, the drug resistance and expression of P-glycoprotein of the transformants were unstable and associated quantitatively with the number of double minute chromosomes. We suggest that the gene for multiple drug resistance and P-glycoprotein is contained in these extrachromosomal particles and is amplified by increases in double minute chromosome number. The potential use of this system for manipulation of mammalian genes in general is discussed.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1 Animals Chromosomes/physiology Colchicine/toxicity DNA/genetics Dactinomycin/toxicity Drug Resistance Gene Amplification Glycoproteins/genetics Karyotyping L Cells/physiology Mice Mutation Puromycin/toxicity Transformation, Genetic
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 Glycoproteins Dactinomycin Puromycin DNA Colchicine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Robertson S M
Ling V
Stanners C P
References (56)
56 references, click to expand
  1. Gene amplification in methotrexate-resistant mouse cells. IV. Different DNA sequences are amplified in different resistant lines.
    Nucleic Acids Res. 1982 Nov 11;10(21):6597-618 PMID: 6294610
  2. DNA-mediated transfer of multiple drug resistance and plasma membrane glycoprotein expression.
    Mol Cell Biol. 1982 Aug;2(8):881-9 PMID: 6127625
  3. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells.
    Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373-6 PMID: 286319
  4. Dominance of colchicine resistance in hybrid CHO cells.
    Somatic Cell Genet. 1978 Mar;4(2):193-200 PMID: 566474
  5. Phenotype stabilisation and integration of transferred material in chromosome-mediated gene transfer.
    Nature. 1979 Aug 23;280(5724):657-60 PMID: 471042
  6. Gene amplification causes overproduction of the first three enzymes of UMP synthesis in N-(phosphonacetyl)-L-aspartate-resistant hamster cells.
    J Biol Chem. 1979 Sep 10;254(17):8679-89 PMID: 381311
  7. Transforming DNA integrates into the host chromosome.
    Cell. 1981 Jan;23(1):29-39 PMID: 7214526
  8. Two types of ribosome in mouse-hamster hybrid cells.
    Nat New Biol. 1971 Mar 10;230(10):52-4 PMID: 5279808
  9. The transfer and stable integration of the HSV thymidine kinase gene into mouse cells.
    Cell. 1978 May;14(1):133-41 PMID: 208776
  10. Loss and stabilization of amplified dihydrofolate reductase genes in mouse sarcoma S-180 cell lines.
    Mol Cell Biol. 1981 Dec;1(12):1084-93 PMID: 7346713
  11. Chromosomal variation and the origin of drug-resistant mutants in mammalian cell lines.
    Proc Natl Acad Sci U S A. 1974 Dec;71(12):5027-31 PMID: 4531035
  12. Plasma membrane proteins and glycoproteins from Chinese hamster cells sensitive and resistant to actinomycin D.
    J Supramol Struct. 1978;9(3):289-98 PMID: 748679
  13. Co-expression and amplification of dihydrofolate reductase cDNA and the Escherichia coli XGPRT gene in Chinese hamster ovary cells.
    J Mol Appl Genet. 1981;1(3):165-75 PMID: 6180118
  14. Studies of 125I trace labeling of immunoglobulin G by chloramine-T.
    Immunochemistry. 1970 Nov;7(11):885-98 PMID: 5531224
  15. Amplification and loss of dihydrofolate reductase genes in a Chinese hamster ovary cell line.
    Mol Cell Biol. 1981 Dec;1(12):1069-76 PMID: 7346712
  16. Cloning of a functional gene responsible for the expression of a cell surface antigen correlated with human chronic lymphocytic leukemia.
    Cell. 1981 Nov;27(1 Pt 2):211-21 PMID: 6459855
  17. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line.
    Proc Natl Acad Sci U S A. 1978 Nov;75(11):5553-6 PMID: 281704
  18. Transformation of mammalian cells with an amplifiable dominant-acting gene.
    Proc Natl Acad Sci U S A. 1980 Jun;77(6):3567-70 PMID: 6251468
  19. Ultrastructure of double minutes from a human tumor cell line.
    J Cell Biol. 1979 Dec;83(3):663-6 PMID: 521457
  20. Cloning of cDNA for argininosuccinate synthetase mRNA and study of enzyme overproduction in a human cell line.
    J Biol Chem. 1981 Nov 25;256(22):11826-31 PMID: 6170638
  21. Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells.
    Cell. 1974 Jul;2(3):173-82 PMID: 4547236
  22. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes.
    Proc Natl Acad Sci U S A. 1979 Nov;76(11):5669-73 PMID: 293670
  23. Stable mutants of mammalian cells that overproduce the first three enzymes of pyrimidine nucleotide biosynthesis.
    Cell. 1976 Dec;9(4 Pt 1):541-50 PMID: 12870
  24. Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts.
    Cancer Res. 1979 Jun;39(6 Pt 1):2070-6 PMID: 571759
  25. Deoxyribonucleic acid-mediated gene transfer in mammalian cells: molecular analysis of unstable transformants and their progression to stability.
    Mol Cell Biol. 1981 Feb;1(2):111-20 PMID: 6100961
  26. Selection of tunicamycin-resistant Chinese hamster ovary cells with increased N-acetylglucosaminyltransferase activity.
    J Cell Biol. 1982 Sep;94(3):586-91 PMID: 6215412
  27. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  28. Correlation of double-minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells.
    Proc Natl Acad Sci U S A. 1981 Jun;78(6):3654-8 PMID: 6943568
  29. Parameters governing the transfer of the genes for thymidine kinase and dihydrofolate reductase into mouse cells using metaphase chromosomes or DNA.
    Somatic Cell Genet. 1980 May;6(3):333-47 PMID: 6931407
  30. Molecular analysis of chromosome-mediated gene transfer.
    Proc Natl Acad Sci U S A. 1979 Aug;76(8):3987-90 PMID: 226993
  31. Relationship of amplified dihydrofolate reductase genes to double minute chromosomes in unstably resistant mouse fibroblast cell lines.
    Mol Cell Biol. 1981 Dec;1(12):1077-83 PMID: 6287217
  32. Overexpression of an unstably inherited gene in cultured mouse cells.
    Proc Natl Acad Sci U S A. 1977 Sep;74(9):3956-9 PMID: 269446
  33. A monoclonal antibody demonstrating specificity for drug-resistance cells.
    Immunol Lett. 1982 Jul;5(1):15-8 PMID: 6180980
  34. Chromosomal and extrachromosomal localization of amplified dihydrofolate reductase genes in cultured mammalian cells.
    Cold Spring Harb Symp Quant Biol. 1981;45 Pt 2:785-97 PMID: 6942951
  35. Genetic and physical linkage of exogenous sequences in transformed cells.
    Cell. 1980 Nov;22(1 Pt 1):309-17 PMID: 6253083
  36. Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells.
    J Biol Chem. 1978 Mar 10;253(5):1357-70 PMID: 627542
  37. THE "INDUCTION" OF DIHYDROFOLIC REDUCTASE ACTIVITY IN LEUKOCYTES AND ERYTHROCYTES OF PATIENTS TREATED WITH AMETHOPTERIN.
    J Clin Invest. 1963 Apr;42(4):466-75 PMID: 16695899
  38. Double minutes in human tumor cells.
    Cancer Genet Cytogenet. 1982 Feb;5(1):81-94 PMID: 6175392
  39. Drug-resistant mutants of Chinese hamster ovary cells possess an altered cell surface carbohydrate component.
    J Supramol Struct. 1976;4(4):521-6 PMID: 933538
  40. Pleiotropic phenotype of colchicine-resistant CHO cells: cross-resistance and collateral sensitivity.
    J Cell Physiol. 1976 May;88(1):23-31 PMID: 57118
  41. Chromosome-mediated transfer and amplification of an altered mouse dihydrofolate reductase gene.
    Somatic Cell Genet. 1982 Jul;8(4):499-508 PMID: 7123452
  42. Drug resistance and membrane alteration in mutants of mammalian cells.
    Can J Genet Cytol. 1975 Dec;17(4):503-15 PMID: 1203765
  43. Reduced permeability in CHO cells as a mechanism of resistance to colchicine.
    J Cell Physiol. 1974 Feb;83(1):103-16 PMID: 4855907
  44. A quick reference chart on cross resistance between anticancer patients.
    Cancer Chemother Rep. 1972 Aug;56(4):493-8 PMID: 5081592
  45. Selection of aphidicolin-resistant CHO cells with altered levels of ribonucleotide reductase.
    Somatic Cell Genet. 1981 Mar;7(2):255-68 PMID: 6794165
  46. Chinese hamster ovary cells resistant to beta-aspartylhydroxamate contain increased levels of asparagine synthetase.
    J Biol Chem. 1980 May 25;255(10):4808-13 PMID: 6102991
  47. Cloning of DNA from double minutes of Y1 mouse adrenocortical tumor cells: evidence for gene amplification.
    Cell. 1981 Apr;24(1):117-23 PMID: 7237541
  48. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.
    Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 PMID: 990323
  49. Daunorubicin-resistant Chinese hamster ovary cells expressing multidrug resistance and a cell-surface P-glycoprotein.
    Cancer Res. 1983 Sep;43(9):4413-9 PMID: 6135505
  50. Amplification of the metallothionein-I gene in cadmium-resistant mouse cells.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2110-4 PMID: 6941274
  51. Experimental chemotherapy of neuroblastoma. II. Increased thymidylate synthetase activity in a 5-fluorodeoxyuridine-resistant variant of mouse neuroblastoma.
    Mol Pharmacol. 1975 Jan;11(1):105-17 PMID: 123312
  52. Increased levels of threonyl-tRNA synthetase in a borrelidin-resistant Chinese hamster ovary cell line.
    Proc Natl Acad Sci U S A. 1981 Sep;78(9):5367-70 PMID: 6946478
  53. Plaque formation and isolation of pure lines with poliomyelitis viruses.
    J Exp Med. 1954 Feb;99(2):167-82 PMID: 13130792
  54. Rapid assays for evaluating the drug sensitivity of tumor cells.
    J Natl Cancer Inst. 1977 Jul;59(1):21-7 PMID: 875055
  55. Alterations in cell surface membranes in Chinese hamster lung cell resistant to adriamycin.
    Biochem Biophys Res Commun. 1982 Mar 15;105(1):157-63 PMID: 7092850
  56. A new technique for the assay of infectivity of human adenovirus 5 DNA.
    Virology. 1973 Apr;52(2):456-67 PMID: 4705382
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.4.3.500-506.1984
Published
1984-03-00
Pages
500-6
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC368728
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.4.3.500-506.1984 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2