Cytostatic Drug Resistance and Differentiation in Friend Erythroleukemia Cells

  • C. A. Schmidt
  • A. Schäfer
  • F. Lorenz
  • H. Oettle
  • F. F. Wilborn
  • D. Huhn
  • W. Siegert
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)

Abstract

Cytostatic drug resistance is a common clinical problem in antitumor chemotherapy. To study mechanisms of drug resistance, in vitro model systems have been established. Frequently cross-resistance to other cytostatic drugs (i.e., chemically and structurally not related to the selective agent) was observed in these cell lines [1]. Multidrug resistance included medicaments often used in clinical therapy regimens such as vinca alkaloids or anthracyclines. Over-expression of a 170 kD glycoprotein was found to correlate with the multidrugresistant phenotype [2, 3]. The gene encoding for the 170 kD glycoprotein, mdrl, has been cloned and sequenced [4, 5]. The multidrug-resistant phenotype could be transferred to drug-sensitive cells by transfection with mdrl cDNA [6, 7]. Resistant cells showed significant lower intracellular cytostatic drug levels, due to an activated drug efflux mechanism [8, 9]. MDR gene overexpression was detected in several leukemias and tumors and could be related to poor prognosis [10–13].

Keywords

Vinca Alkaloid Cytostatic Drug Multidrug Resis Ling Versus Actin Probe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    McGrath T, Latoud C, Arnold ST, Safa A, Felsted R, Center M (1989) Mechanisms of multidrug resistance in HL 60 cells. Biochem Pharmacol 38: 3611–3619PubMedCrossRefGoogle Scholar
  2. 2.
    Beck WT, Mueller TJ, Tanzer LR (1975) Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res 39: 2070–2076Google Scholar
  3. 3.
    Riordan JR, Deuchars K, Kartner N, Alon N, Trent J, Ling V (1985) Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 316: 817–819PubMedCrossRefGoogle Scholar
  4. 4.
    Van der Bliek AM, Baas F, Van der VeldeKoerts T, Biedler JL, Myers MB, Ozols RF, Hamilton TC, Joenje H, Borst P (1988) Genes amplified and overexpressed in human multidrug resistant cell lines. Cancer Res 48: 5927–5932PubMedGoogle Scholar
  5. 5.
    Ueda K, Clark DP, Chen LJ, Roninson IB, Gottesman MM, Pastan I (1987) The human multidrug resistance (MDR1) gene: cDNA cloning and transcription initiation. J Biol Chem 262: 505–508PubMedGoogle Scholar
  6. 6.
    Ueda K, Cornwell MM, Pastan I, Roninson IB, Ling V, Riordan JR (1986) The mdrl gene responsible for multidrug resistance, codes for P-glycoprotein. Biochem Biophys Res Commun 141: 956PubMedCrossRefGoogle Scholar
  7. 7.
    Ueda K, Cardarelli C, Gottesman MM, Pastan I (1987) Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, adriamycin, and vinblastine. Proc Natl Acad Sci USA 84: 3004–3008PubMedCrossRefGoogle Scholar
  8. 8.
    Gros P, NeriahYB, Croop JM, Housman DE (1986) Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 323: 728–731PubMedCrossRefGoogle Scholar
  9. 9.
    Cornwell MM, Tsuruo T, Gottesman MM, Pastan I (1987) ATP-binding properties of P-glycoprotein from multidrug resistant KB cells. FASEB J 1: 51–54PubMedGoogle Scholar
  10. 10.
    Inaba M, Johnson RK (1987) Uptake and retention of adriamycin and daunorubicin by sensitive and anthracycline resistant sublines of P388 leukemia. Biochem Pharmacol 27: 2123–2130CrossRefGoogle Scholar
  11. 11.
    Gros P, Croop J, Housman DE (1986) Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47: 371–380PubMedCrossRefGoogle Scholar
  12. 12.
    Sato H, Preisler HD, Gottesman MM, Leukemia Intergroup (1988) Expression of the multidrug resistance gene (mdr) in the cells of patients with ANLL. Blood 72 (5/Suppl 1): 224aGoogle Scholar
  13. 13.
    Sato H, Gottesman MM, Goldstein LJ, Pas-tan I, Block AM, Sanberg AA, Preisler HD (1990) Expression of the multidrug resistance gene in myeloid leukemias. Leuk Res 44: 11–22CrossRefGoogle Scholar
  14. 14.
    Steinheider G, Westendorf J, Marquardt H (1986) Induction of differentiation by the anthracycline antitumor antibiotics, Aclacinomycin A, Musettamycin and Marcellomycin. Leuk Res 10: 1233–1239PubMedCrossRefGoogle Scholar
  15. 15.
    Ostertag W, Melderis H, Steinheider G, Kluge N, Dube SK (1972) Synthesis of mouse haemoglobin and globin mRNA in leukemic cell cultures. Nature N Biol 239: 231Google Scholar
  16. 16.
    Maniatis T, Fritsch EF, Sambrook J (1982) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • C. A. Schmidt
    • 1
  • A. Schäfer
    • 2
  • F. Lorenz
    • 1
  • H. Oettle
    • 1
  • F. F. Wilborn
    • 1
  • D. Huhn
    • 1
  • W. Siegert
    • 1
  1. 1.Universitätsklinikum Rudolf Virchow, Abtlg Innere MedizinFreie Universität BerlinBerlinGermany
  2. 2.Abtlg ToxikologieUniversität HamburgHamburgGermany

Personalised recommendations