Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 Dec;7(12):4549–4552. doi: 10.1128/mcb.7.12.4549

Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

Y Sugimoto 1, I B Roninson 1, T Tsuruo 1
PMCID: PMC368140  PMID: 3481435

Abstract

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.

Full text

PDF

Images in this article

4550Image
on p.4550

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck W. T., Mueller T. J., Tanzer L. R. Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res. 1979 Jun;39(6 Pt 1):2070–2076. [PubMed] [Google Scholar]
  2. Chen C. J., Chin J. E., Ueda K., Clark D. P., Pastan I., Gottesman M. M., Roninson I. B. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381–389. doi: 10.1016/0092-8674(86)90595-7. [DOI] [PubMed] [Google Scholar]
  3. Cornwell M. M., Safa A. R., Felsted R. L., Gottesman M. M., Pastan I. Membrane vesicles from multidrug-resistant human cancer cells contain a specific 150- to 170-kDa protein detected by photoaffinity labeling. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3847–3850. doi: 10.1073/pnas.83.11.3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Gerlach J. H., Endicott J. A., Juranka P. F., Henderson G., Sarangi F., Deuchars K. L., Ling V. Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature. 1986 Dec 4;324(6096):485–489. doi: 10.1038/324485a0. [DOI] [PubMed] [Google Scholar]
  7. Gros P., Ben Neriah Y. B., Croop J. M., Housman D. E. Isolation and expression of a complementary DNA that confers multidrug resistance. Nature. 1986 Oct 23;323(6090):728–731. doi: 10.1038/323728a0. [DOI] [PubMed] [Google Scholar]
  8. Gros P., Croop J., Housman D. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell. 1986 Nov 7;47(3):371–380. doi: 10.1016/0092-8674(86)90594-5. [DOI] [PubMed] [Google Scholar]
  9. Gros P., Croop J., Roninson I., Varshavsky A., Housman D. E. Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proc Natl Acad Sci U S A. 1986 Jan;83(2):337–341. doi: 10.1073/pnas.83.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gros P., Fallows D. A., Croop J. M., Housman D. E. Chromosome-mediated gene transfer of multidrug resistance. Mol Cell Biol. 1986 Nov;6(11):3785–3790. doi: 10.1128/mcb.6.11.3785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hamada H., Tsuruo T. Functional role for the 170- to 180-kDa glycoprotein specific to drug-resistant tumor cells as revealed by monoclonal antibodies. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7785–7789. doi: 10.1073/pnas.83.20.7785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Juliano R. L., Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976 Nov 11;455(1):152–162. doi: 10.1016/0005-2736(76)90160-7. [DOI] [PubMed] [Google Scholar]
  13. Kartner N., Riordan J. R., Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science. 1983 Sep 23;221(4617):1285–1288. doi: 10.1126/science.6137059. [DOI] [PubMed] [Google Scholar]
  14. Nakajima-Iijima S., Hamada H., Reddy P., Kakunaga T. Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6133–6137. doi: 10.1073/pnas.82.18.6133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peterson R. H., Meyers M. B., Spengler B. A., Biedler J. L. Alteration of plasma membrane glycopeptides and gangliosides of Chinese hamster cells accompanying development of resistance to daunorubicin and vincristine. Cancer Res. 1983 Jan;43(1):222–228. [PubMed] [Google Scholar]
  16. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  17. Riordan J. R., Deuchars K., Kartner N., Alon N., Trent J., Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. 1985 Aug 29-Sep 4Nature. 316(6031):817–819. doi: 10.1038/316817a0. [DOI] [PubMed] [Google Scholar]
  18. Roninson I. B., Abelson H. T., Housman D. E., Howell N., Varshavsky A. Amplification of specific DNA sequences correlates with multi-drug resistance in Chinese hamster cells. Nature. 1984 Jun 14;309(5969):626–628. doi: 10.1038/309626a0. [DOI] [PubMed] [Google Scholar]
  19. Roninson I. B., Chin J. E., Choi K. G., Gros P., Housman D. E., Fojo A., Shen D. W., Gottesman M. M., Pastan I. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4538–4542. doi: 10.1073/pnas.83.12.4538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Roninson I. B. Detection and mapping of homologous, repeated and amplified DNA sequences by DNA renaturation in agarose gels. Nucleic Acids Res. 1983 Aug 25;11(16):5413–5431. doi: 10.1093/nar/11.16.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Safa A. R., Glover C. J., Meyers M. B., Biedler J. L., Felsted R. L. Vinblastine photoaffinity labeling of a high molecular weight surface membrane glycoprotein specific for multidrug-resistant cells. J Biol Chem. 1986 May 15;261(14):6137–6140. [PubMed] [Google Scholar]
  22. Scotto K. W., Biedler J. L., Melera P. W. Amplification and expression of genes associated with multidrug resistance in mammalian cells. Science. 1986 May 9;232(4751):751–755. doi: 10.1126/science.2421411. [DOI] [PubMed] [Google Scholar]
  23. Shen D. W., Fojo A., Chin J. E., Roninson I. B., Richert N., Pastan I., Gottesman M. M. Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification. Science. 1986 May 2;232(4750):643–645. doi: 10.1126/science.3457471. [DOI] [PubMed] [Google Scholar]
  24. Shen D. W., Fojo A., Roninson I. B., Chin J. E., Soffir R., Pastan I., Gottesman M. M. Multidrug resistance of DNA-mediated transformants is linked to transfer of the human mdr1 gene. Mol Cell Biol. 1986 Nov;6(11):4039–4045. doi: 10.1128/mcb.6.11.4039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  26. Tsuruo T., Iida-Saito H., Kawabata H., Oh-hara T., Hamada H., Utakoji T. Characteristics of resistance to adriamycin in human myelogenous leukemia K562 resistant to adriamycin and in isolated clones. Jpn J Cancer Res. 1986 Jul;77(7):682–692. [PubMed] [Google Scholar]
  27. Tsuruo T., Iida H., Ohkochi E., Tsukagoshi S., Sakurai Y. Establishment and properties of vincristine-resistant human myelogenous leukemia K562. Gan. 1983 Oct;74(5):751–758. [PubMed] [Google Scholar]
  28. Tsuruo T., Oh-Hara T., Saito H. Characteristics of vincristine resistance in vincristine resistant human myelogenous leukemia K562. Anticancer Res. 1986 Jul-Aug;6(4):637–641. [PubMed] [Google Scholar]
  29. Ueda K., Cornwell M. M., Gottesman M. M., Pastan I., Roninson I. B., Ling V., Riordan J. R. The mdr1 gene, responsible for multidrug-resistance, codes for P-glycoprotein. Biochem Biophys Res Commun. 1986 Dec 30;141(3):956–962. doi: 10.1016/s0006-291x(86)80136-x. [DOI] [PubMed] [Google Scholar]
  30. Van der Bliek A. M., Van der Velde-Koerts T., Ling V., Borst P. Overexpression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line. Mol Cell Biol. 1986 May;6(5):1671–1678. doi: 10.1128/mcb.6.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. de Bruijn M. H., Van der Bliek A. M., Biedler J. L., Borst P. Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines. Mol Cell Biol. 1986 Dec;6(12):4717–4722. doi: 10.1128/mcb.6.12.4717. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES