Skip to main content
SpringerLink
Log in
Book cover

Molecular and Clinical Advances in Anticancer Drug Resistance pp 101–119Cite as

Expression of the MDR1 gene in human cancers

  • Chapter

Part of the book series: Cancer Treatment and Research ((CTAR,volume 57))

Abstract

Although chemotherapy can result in the cure of many malignancies, such as testicular cancer, Hodgkin’ s disease, and childhood leukemias, we are continually faced with the obstacle of tumors that respond poorly to chemotherapy, such as non-small-cell lung cancer and gastrointestinal malignancies. In addition, there are many cancers, such as breast cancer and non-Hodgkins lymphoma, that initially may respond to chemotherapy and then relapse either during or after therapy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. DeVita, V.T. Principles of chemotherapy. In: Cancer Principles and Practice of Oncology, DeVita, V.T., Hellman, S., and Rosenberg, S.A. (eds). J.B. Lippincott, Philadelphia, pp. 276–298, 1989.

    Google Scholar 

  2. Hyrnink, W.M. The importance of dose intensity in the outcome of chemotherapy. In: Improved Advances in Oncology, DeVita, V.T., Hellman, S., and Rosenberg, S.A. (eds). J.B. Lippincott, Philadelphia, pp. 121–142, 1988.

    Google Scholar 

  3. Biedler, J.L. and Riehm, H. Cellular resistance to actinomycin D in Chinese hamster ovary cells in vitro: cross-resistance, radiographic and cytogenetic studies. Cancer Res. 30:1174–1184, 1970.

    PubMed  CAS  Google Scholar 

  4. Ling, V. and Thompson, L.H. Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J. Cell Physiol. 83:103–116, 1973.

    Article  Google Scholar 

  5. Beck, W.T., Mueller, T.J., and Tanzer, L.R. Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res. 39:2070–2076, 1979.

    PubMed  CAS  Google Scholar 

  6. Akiyama, S., Fojo, A., Hanover, J.A., Pastan, I., and Gottesman, M.M. Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat. Cell Mol. Genet. 11:117–126, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. Shen, D.-W., Cardarelli, C, Hwang, J., Richert, N., Pastan, I., and Gottesman, M.M. Multiple drug resistant human KB carcinoma cells independently selected for high level resistance to colchicine, adriamycin or vinblastine show changes in expression of specific proteins. J. Biol. Chem. 261:7762–7770, 1986.

    PubMed  CAS  Google Scholar 

  8. Fojo, A., Akiyama, S.I., Gottesman, M.M., and Pastan, I. Reduced drug accumulation in multiply drug-resistant human KB carcinoma cell lines. Cancer Res. 45:3002–3007, 1985.

    PubMed  CAS  Google Scholar 

  9. Shen, D.-W., Fojo, A., Chin, J.E., Roninson, I.B., Richert, N., Pastan, I., and Gottesman, M.M. Human multidrug-resistant cell lines: increased mdrl expression can precede gene amplification. Science 232:643–645, 1986.

    Article  PubMed  CAS  Google Scholar 

  10. Riordan, J.R., Deuchars, K., Kartner, N., et al. Amplification of P-glycoprotein genes in multidrug resistant mammalian cell lines. Nature 316:817–819, 1985.

    Article  PubMed  CAS  Google Scholar 

  11. Van der Bliek, A.M., Van der Velde-Koerts, I., Ling, V., and Borst, P. Overexpression and amplification of five genes in a multidrug-resistant Chinese hamster ovary cell line. Mol. Cell Biol. 6:1671–1687, 1986.

    PubMed  Google Scholar 

  12. Scotto, K.W., Biedler, J., and Melera, P.W. Amplification and expression of genes associated with multidrug resistance in mammalian cells. Science 232:751–755, 1986.

    Article  PubMed  CAS  Google Scholar 

  13. Gros, P., Croop, J., Roninson, I., Varshavsky, A., and Housman, D.E. Isolation and characterization of DNA sequences amplified in multidrug-resistant hamster cells. Proc. Natl. Acad. Sci. USA 83:337–341, 1986.

    Article  PubMed  CAS  Google Scholar 

  14. Roninson, I.B., Chin, J.E., Choi, K., Gros, P., Housman, D.E., Fojo, A., Shen, D.-W., Gottesman, M.M., and Pastan, I. Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells. Proc. Natl. Acad. Sci. USA 83:4538–4542, 1986.

    Article  PubMed  CAS  Google Scholar 

  15. Horio, M., Gottesman, M.M., and Pastan, I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc. Natl. Acad. Sci. USA 185:3580–3584, 1988.

    Article  Google Scholar 

  16. Gottesman, M.M., and Pastan, I. The multidrug transporter: a double edged sword. J. Biol. Chem. 263:12163–12166, 1988.

    PubMed  CAS  Google Scholar 

  17. Endicott, J. and Ling, V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev. Biochem. 58:137–171, 1989.

    Article  PubMed  CAS  Google Scholar 

  18. Croop, J.M., Gros, P., and Housman, D.E. Genetics of multidrug resistance. J. Clin. Invest. 81:1303–1309, 1988.

    Article  PubMed  CAS  Google Scholar 

  19. Ueda, K., Clark, D.P., Chen, C.J., Roninson, I.B., Gottesman, M.M., and Pastan, I. The human multidrug resistance (mdrl) gene, cDNA cloning and transcription initiation. J. Biol. Chem. 262:505–508, 1987.

    PubMed  CAS  Google Scholar 

  20. Fojo, A., Ueda, K., Slamon, D.J., Poplack, D.G., Gottesman, M.M., and Pastan, I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Natl. Acad. Sci. USA 84:265–269, 1987.

    Article  PubMed  CAS  Google Scholar 

  21. Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., and Pastan, I. Cellular localization of the multidrug-resistant gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 84:7735–7738, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Cordon-Cardo, C., O’Brien, J.P., Casals, D., Rittman-Graner, L., Beidler, J.L., Melamed, M.R., and Bertino J.R. Multidrug-resistance gene (p-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. USA 86:695–698, 1989.

    Article  PubMed  CAS  Google Scholar 

  23. Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I., and Willingham, M.C. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein, P170: evidence for localization in brain capillaries and cross-reactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 37:159–164, 1989.

    Article  PubMed  CAS  Google Scholar 

  24. Sugawara, I., Kataoka, I., Morishita, Y., Hamada, H., Tsuruo, T., Itayama, S., and Mori, S. Tissue distribution of P-glycoprotein encoded by a multidrug resistant gene as revealed by a monoclonal antibody, MRK16._Cancer Res. 48:4611–4614, 1988.

    PubMed  CAS  Google Scholar 

  25. Gros, P., Ben Neriah, Y., Croop, J.M., and Housman, D.E. Isolation and expression of a complementary DNA that confers multidrug resistance. Nature 323:728–731, 1986.

    Article  PubMed  CAS  Google Scholar 

  26. Ueda, K., Cardarelli, C, Gottesman, M.M., and Pastan, I. Expression of a full-length cDNA for the human mdrl gene confers resistance to colchicine, doxorubicin and vinblastine. Proc. Natl. Acad. Sei. USA 84:3004–3008, 1987.

    Article  CAS  Google Scholar 

  27. Guild, B.C., Mulligan, R.C., Gros, P., and Housman, D.E. Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection. Proc. Natl. Acad. Sei. USA 85:1595–1599, 1988.

    Article  CAS  Google Scholar 

  28. Pastan, I., Gottesman, M.M., Ueda, K., Lovelace, E., Rutherford, A.V., and Willingham, M.C. A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc. Natl. Acad. Sci. USA 85:4486–4490, 1988.

    Article  PubMed  CAS  Google Scholar 

  29. Kakehi, Y., Kanamaru, H., Yoshida, O., Ohkubo, H., Nakanishi, S., Gottesman, M.M., and Pastan, I. Measurement of multidrug resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance. J. Urol. 139:862–865, 1988.

    PubMed  CAS  Google Scholar 

  30. Fojo, A.T., Shen, D.-W., Mickley, L.A., Pastan, I., and Gottesman, M.M. Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug resistance gene. J. Clin. Oncol. 5:1922–1927, 1987.

    PubMed  CAS  Google Scholar 

  31. Galski, H., Sullivan, M., Willingham, M.C., Chin, K.V., Gottesman, M.M., Pastan, I., and Merlino, G. Expression of a human multidrug resistance cDNA (MDR1) in the bone marrow of transgenic mice: resistance to daunomycin-induced leukopenia. Mol. Cell Biol. 9:4357–4363, 1989.

    PubMed  CAS  Google Scholar 

  32. Salmon, S.E., Grogan, T.M., Miller, T., Scheper, R., and Dalton, W.S. Prediction of doxorubicin-resistance in vitro in myeloma, lymphoma and breast cancer by P-glycoprotein staining. J. Natl. Cancer Inst. 81:696–701, 1989.

    Article  PubMed  CAS  Google Scholar 

  33. Bates, S.E., Mickley, L.A., Chen, Y.-N., Richert, N., Rudick, J., Biedler, J.L., and Fojo, A.T. Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid induced differentiation. Mol. Cell. Biol. 9:4337–4344, 1989.

    PubMed  CAS  Google Scholar 

  34. Chin, K.-V., Tanaka, S., Darlington, G., Pastan, I., and Gottesman, M.M. Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells. J. Biol. Chem., in press.

    Google Scholar 

  35. Gottesman, M.M., Goldstein, L.J., Bruggemann, E., Currier, S., Galski, H., Cardarelli, C, Thiebaut, F., Willingham, M.C., and Pastan, I. Molecular diagnosis of multidrug resistance. In: Cancer Cells, Vol. 7; Molecular Diagnosis of Human Cancer, Furth, M. and Greaves, M. (eds). Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989.

    Google Scholar 

  36. Chirgwin, J., Przybyla, A., MacDonald, R., and Rutter, W.J. Isolation of biologically active ribonucleotide acid sources enriched in ribonuclease. Biochemistry 18:5294–5299, 1976.

    Article  Google Scholar 

  37. Chomezynski, P. and Sacchi, N. Single step method of RNA isolation by acid quanidium thiocynate-phenolchloroform extracted. Anal. Biochem. 162:156–159, 1987.

    Google Scholar 

  38. Goldstein, L.J., Galski, H., Fojo, A., Willingham, M., Lai, S., Gazdar, A., Pirker, R., Green, A., Crist, W., Brodeur, G., Lieber, M., Cossman, J., Gottesman, M.M., and Pastan, I. Expression of a multidrug resistance gene in human cancers. J. Natl. Cancer Inst. 81:116–124, 1989.

    Article  PubMed  CAS  Google Scholar 

  39. Wallace, A.C. and Nairn, P.C. Renal tubular antigens in kidney tumors. Cancer 29: 977–981, 1972.

    Article  PubMed  CAS  Google Scholar 

  40. Mickley, F. and Fojo, A.T. In situ detection of MDR1 RNA in normal human tissues, submitted, 1989.

    Google Scholar 

  41. Kanamaru, H., Kakehi, Y., Yoshida, O., Nakanishi, S., Pastan, I., and Gottesman, M.M. MDR1 RNA levels in human renal cell carcinomas: correlation with grade and prediction of reversal of doxorubicin resistance by quinidine in tumor explants. J. Natl. Cancer Inst. 81:844–849, 1989.

    Article  PubMed  CAS  Google Scholar 

  42. Cancer Facts and Figures. American Cancer Society, 1988.

    Google Scholar 

  43. Grem, J.L. 5-fluorouracil plus leucovorin in cancer therapy. In: Principles and Practice of Oncology Update, Vol. 2, DeVita, V.T., Hellman, S., and Rosenberg, S.A. (eds). J.B. Lippincott, Philadelphia,p. 7, 1988.

    Google Scholar 

  44. Laurie, J.A., Moertel, C G., Fleming, T.R., Wiend, H.S.M., Leigh, J.E., Rubin, J., McCormack, G.W., Gerstner, J.B., Krook, J.E., Malliard, J., Twito, D.T., Morton, R.F., Tschetter, L.K., and Barlow, J.F. Surgical adjuvant therapy of large bowel carcinoma: an evaluation of levamisole and the combination of levamisole and 5-fluorouracil. A study of the North Central Cancer Treatment Group and Mayo Clinic.J. Clin. Oncol. 7:1447–1456, 1989.

    PubMed  CAS  Google Scholar 

  45. Carter, S.F. and Friedman, M. Integration of chemotherapy with combined modality treatment of solid tumors. II. Large bowel carcinoma. Cancer Treat. Rev. 1:111–129, 1974.

    Article  Google Scholar 

  46. Van Sloten, K., Wiernik, P.H., Schiffer, C A., and Schimpf, S.C. Evaluation of levamisole as an adjuvant to chemotherapy for treatment of ANLL. Cancer 51:1576, 1983.

    Article  PubMed  Google Scholar 

  47. Sato, H., Preisler, H., Day, R., Raza, A., Larson, R., Browman, A., Goldberg, J., Wagler, R., Grunwald, H., Gottlieb, A., Bennett, J., Gottesman, M.M., and Pastan, I. MDR1 transcript levels as an indication of resistant disease in acute nonlymphocytic leukemia, B.J. Haematol. 75:340–345, 1990.

    Article  CAS  Google Scholar 

  48. Sato, H., Gottesman, M.M., Goldstein, L.J., Pastan, I., Preisler, H.D., Block, A.M., and Sandberg, A.A. Expression of the multidrug resistance gene in myeloid leukemias. Leuk. Res., 14:11–22, 1990.

    Article  PubMed  CAS  Google Scholar 

  49. Pirker, R., Goldstein, L.J., Ludwig, H., Linkesch, W., Lechner, C, Gottesman, M.M., and Pastan, I. Expression of a multidrug resistance gene in blast crisis of chronic myelogenous leukemia. Cancer Commun. 1:141–144, 1989.

    PubMed  CAS  Google Scholar 

  50. Goldstein, L.J., Fojo, A., Ueda, K., Crist, W., Green, A., Brodeur, A., Pastan, I., and Gottesman, M.M. Expression of the multidrug-resistance (MDR1) gene in neuroblastoma. J. Clin. Oncol., 8:128–136, 1989.

    Google Scholar 

  51. Bourhis, J., Bénard, J., Hartmann, O., Boccon-Gibod, L., Lemerle, J., and Riou, G. Correlation of MDR1 gene expression with chemotherapy in neuroblastoma. J. Natl. Cancer Inst. 81:1401–1405, 1989.

    Article  PubMed  CAS  Google Scholar 

  52. Gerlach, J.H., Bell, D.R., Karakousis, Slocum, H.K., Kartner, N., Rustum, Y.M., Ling, V., and Baker, R.M. P-glycoprotein in human, sarcoma: evidence for multidrug resistance. J. Clin. Oncol. 5:1452–1460, 1987.

    PubMed  CAS  Google Scholar 

  53. Lai, S.L., Goldstein, L.J., Gottesman, M.M., Pastan, I., Tsai, CM., Johnson, B.E., Mulshine, J.L., Ihde, D.C., Kayser, K., and Gazdar, A. MDR1 expression in lung cancer. J. Natl. Cancer Inst. 81:1144–1150, 1989.

    Article  PubMed  CAS  Google Scholar 

  54. Minna, J.P., Pass, H., Glatstein, E.J., and Ihde, D.C. Cancer of the lung. In Cancer: Principles and Practice of Oncology, De Vita, V.T., Hellman, S., and Rosenberg, S.A. (eds). J.B. Lippincott, Philadelphia, pp. 591–688, 1989.

    Google Scholar 

  55. Merkel, D.E., Fugua, S.A.W., Tandona, A.K., Hill, S.M., Buzdar, A.V., and MaGuire, W.L. Electrophoretic analysis of 248 clinical breast specimens for P-GP overexpression or gene amplification. J. Clin. Oncol. 7:1129–1136, 1989.

    PubMed  CAS  Google Scholar 

  56. Keith, W.N., Stallard, S., and Brown, R. Expression of mdrl and gst-pi in human breast tumors: comparison to in vitro chemosensitivity, submitted.

    Google Scholar 

  57. Ma, D.D., Davey, R.A., Harman, D.A., Isbister, J.P., Scurr, R.D., Mackertich, S.M., Dowden, C, and Bell, D.R. Detection of a multidrug resistant phenotype in acute non-lymphoblastic leukemia. Lancet 1:135–137, 1987.

    Article  PubMed  CAS  Google Scholar 

  58. Ito, Y., Tanimoto, M., Kumazawa, T., Okumura, M., Monshima, Y., Ohno, R., and Saito, H. Increased P-glycoprotein expression and multidrug-resistant gene (mdrl) amplification are infrequently found in fresh acute leukemia cells. Sequential analysis of 15 cases at initial presentation and relapsed stage. Cancer 63:1534–1538, 1989.

    CAS  Google Scholar 

  59. Salmon, S.E., Grogan, T.M., Miller, T., Scheper, K., and Dalton, W.S. Prediction of doxorubicin resistance in vitro in myeloma, lymphoma, and breast cancer by P-glycoprotein staining. J. Natl. Cancer Inst. 81:696–701, 1989.

    Article  PubMed  CAS  Google Scholar 

  60. Fojo, A., Cornwell, M., Cardarelli, CO., Clark, D.P., Richert, N., Shen, D.-W., Ueda, K., Willingham, M.C., Gottesman, M.M., and Pastan, I. Molecular biology of drug resistance. Breast Cancer Res. Treat. 8:5–16, 1987.

    Article  Google Scholar 

  61. Moscow, J.A., Fairchild, C.R., Madden, M.J., Ransom, D.T., Wieand, H.S., O’Brien, E.E., Poplack, D.G., Cossman, J., Myers, CE., and Cowan, K.H. Expression in anionic glutathione S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 49:1422–1428, 1989.

    PubMed  CAS  Google Scholar 

  62. Fredericks, W., Murawski, H., Slocum, H., Gerlach, J., Ling, V., and Baker, R. Incidence of elevated P-glycoprotein in human tumors (abstr.). Proc. Am. Assoc. Cancer Res. 9:302, 1988.

    Google Scholar 

  63. Bell, D.R., Gerlach, J.H., Kartner, N., Buick, R.N., and Ling, V. Detection of P-glycoprotein in ovarian cancer: a molecular marker associated with multidrug resistance. J. Clin. Oncol. 3:311–315, 1985.

    PubMed  CAS  Google Scholar 

  64. Bourhis, J., Goldstein, L.J., Riou, G., Pastan, I., Gottesman, M.M., and Bénard, J. Expression of a human multidrug resistance gene in ovarian carcinomas. Cancer Res. 49:5062–5065, 1989.

    PubMed  CAS  Google Scholar 

  65. Rogan, A.M., Hamilton, T.C., Young, R.C., Klecker, R.W., and Ozols, R.F. Reversal of adriamycin resistance by verapamil in human ovarian cancer. Science 224:994–996, 1984.

    Article  PubMed  CAS  Google Scholar 

  66. Ozols, R.F., Cunnion, R.E., Klecker, R.W., Hamilton, T.C., Ostchega, Y., Parrillo, J.C., and Young, R.C. Verapamil and adriamycin in the treatment of drug-resistant ovarian cancer patients. J. Clin. Oncol. 5:641–647, 1987.

    PubMed  CAS  Google Scholar 

  67. Dalton, W.S., Grogan, T.M., Meltzer, P.S., Scheper, R.J., Durie, B.G., Taylor, C.W., Miller, T.P., and Salmon, S.E. Drug resistance in multiple myeloma and non-Hodgkins lymphoma: detection of P-glycoprotein and potential circumvention by addition of verapamil to chemotherapy. J. Clin. Oncol. 7:415–424, 1989.

    PubMed  CAS  Google Scholar 

  68. Roninson, I.B., Patel, M.C., Lee, I., et al. Molecular mechanisms and diagnostics of multidrug resistance in human tumor cells. In: Cancer Cells, Vol. 7, Furth, M. and Greaves, M. (eds). Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989.

    Google Scholar 

  69. Rapollee, D.A., Marks, D., Branda, M.J., and Werb, Z. Wound macrophages express TGFa and other growth factors in vivo: analysis by mRNA phenotyping. Science 241: 708–711, 1988.

    Article  Google Scholar 

  70. FitzGerald, D.J., Willingham, M.C., Cardarelli, CO., Hamada, H., Tsuruo, T., Gottesman, M.M., and Pastan, I. A monoclonal Ab-Pseudomonas toxin conjugated that specifically kills multidrug-resistant cells. Proc. Natl. Acad. Sci. USA 84:4288–4297, 1987.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Lori J. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael M. Gottesman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ira Pastan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fox Chase Cancer Center, USA

    Robert F. Ozols

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Goldstein, L.J., Gottesman, M.M., Pastan, I. (1991). Expression of the MDR1 gene in human cancers. In: Ozols, R.F. (eds) Molecular and Clinical Advances in Anticancer Drug Resistance. Cancer Treatment and Research, vol 57. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3872-1_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3872-1_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6726-0

  • Online ISBN: 978-1-4615-3872-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation