Biochemistry (Moscow)

, Volume 83, Issue 7, pp 779–786 | Cite as

Recent Advances in the Studies of Molecular Mechanisms Regulating Multidrug Resistance in Cancer Cells

  • A. A. StavrovskayaEmail author
  • E. Yu. Rybalkina


Abstract—Here we present new approaches to better understanding multidrug resistance (MDR) development in cancer cells, such as identification of components of a complex process of MDR evolution. Recent advances in the studies of MDR are discussed: 1) chemotherapy agents might be involved in the selection of cancer stem cells resulting in the elevated drug resistance and enhanced tumorigenicity; 2) cell–cell interactions have a great effect on the MDR emergence and evolution; 3) mechanotransduction is an important signaling mechanism in cell–cell interactions; 4) proteins of the ABC transporter family which are often involved in MDR might be transferred between cells via microvesicles (epigenetic MDR regulation); 5) proteins providing cell-to-cell transfer of functional P-glycoprotein (MDR1 protein) via microvesicles have been investigated; 6) P-glycoprotein may serve to regulate apoptosis, as well as transcription and translation of target genes/proteins. Although proving once again that MDR is a complex multi-faceted process, these data open new approaches to overcoming it.


multidrug resistance cell–cell interactions epigenetic regulation microvesicles 



ATP binding cassette


cancer-associated fibroblasts


cancer stem cells


drug resistance




extracellular matrix


Ewing sarcoma


multidrug resistance


multidrug resistance gene 1, encodes Pgp




normal fibroblasts


P-glycoprotein (according to the current ABCB1 classification)


tumor necrosis factor


TNF-related apoptosis-inducing ligand


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gottesman, M. M. (2002) Mechanisms of cancer drug resistance, Annu. Rev. Med., 53, 615–627.CrossRefPubMedGoogle Scholar
  2. 2.
    Gottesman, M. M., Lavi, O., Hall, M. D., and Gillet, J.–P. (2016) Toward a better understanding of the complexity of cancer drug resistance, Annu. Rev. Pharmacol. Toxicol., 56, 85–102.CrossRefPubMedGoogle Scholar
  3. 3.
    Gay, L., Baker, A.–M., and Graham, T. A. (2016) Tumour cell heterogeneity, F1000Research, 5, 238.CrossRefGoogle Scholar
  4. 4.
    Wind, N. S., and Holen, I. (2011) Multidrug resistance in breast cancer: from in vitro models to clinical studies, Int. J. Breast Cancer, 2011, 967419.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Coley, H. M. (2010) Overcoming multidrug resistance in cancer: clinical studies of P–glycoprotein inhibitors, Methods Mol. Biol., 596, 341–358.CrossRefPubMedGoogle Scholar
  6. 6.
    Thompson, P. A., Kantarjian, H. M., and Cortes, J. E. (2015) Diagnosis and treatment of chronic myeloid leukemia in 2015, Mayo Clin. Proc., 90, 1440–1454.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Higgins, C. F. (2007) Multiple molecular mechanisms for multidrug resistance transporters, Nature, 446, 749–757.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhao, Y., Butler, E. B., and Tan, M. (2013) Targeting cel–lular metabolism to improve cancer therapeutics, Cell Death Dis., 4, e532.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Stavrovskaya, A. A., Stromskaya, T. P., Rybalkina, E. Y., Moiseeva, N. I., Guryanov, S. G., Ovchinnikov, L. P., and Guens, G. P. (2012) YB–1 protein and multidrug resistance of tumor cells, Curr. Signal Transduct. Ther., 7, 237–246.CrossRefGoogle Scholar
  10. 10.
    Flach, E. H., Rebecca, V. W., Herlyn, M., Smalley, K. S. M., and Anderson, A. R. A. (2011) Fibroblasts contribute to melanoma tumor growth and drug resistance, Mol. Pharm., 8, 2039–2049.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L., and Nelson, P. S. (2012) Treatment–induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B, Nat. Med., 18, 1359–1368.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Oesper, L., Satas, G., and Raphael, B. J. (2014) Quantifying tumor heterogeneity in whole–genome and whole–exome sequencing data, Bioinformatics, 30, 3532–3540.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Esparza–Lopez, J., Escobar–Arriaga, E., Soto–Germes, S., and Ibarra–Sanchez, M. J. (2017) Breast cancer intra–tumor heterogeneity: one tumor, different entities, Rev. Invest. Clin., 69, 66–76.PubMedGoogle Scholar
  14. 14.
    Hanahan, D., and Weinberg, R. A. (2011) Hallmarks of cancer: the next generation, Cell, 4, 646–674.CrossRefGoogle Scholar
  15. 15.
    Audia, A., Conroy, S., Glass, R., and Bhat, K. P. L. (2017) The impact of the tumor microenvironment on the proper–ties of glioma stem–like cells, Front. Oncol., 7, 143.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bhowmick, N. A., and Moses, H. L. (2005) Tumor–stroma interactions, Curr. Opin. Genet. Dev., 15, 97–101.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Itoh, G., Chida, S., Yanagihara, K., Yashiro, M., Aiba, N., and Tanaka, M. (2017) Cancer–associated fibroblasts induce cancer cell apoptosis that regulates invasion mode of tumours, Oncogene, 36, 4434–4444.CrossRefPubMedGoogle Scholar
  18. 18.
    Luria, S. E., and Delbuck, M. (1943) Mutations of bacteria from virus ensitivity to virus resistance, Genetics, 28, 491–511.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Ciurea, M. E., Georgescu, A. M., Purcaru, S. O., Artene, S.–A., Emami, G. H., Boldeanu, M. V., Tache, D. E., and Dricu, A. (2014) Cancer stem cells: biological functions and therapeutically targeting, Int. J. Mol. Sci., 15, 8169–8185.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Di, C., and Zhao, Y. (2015) Multiple drug resistance due to resistance to stem cells and stem cell treatment progress in cancer, Exp. Ther. Med., 9, 289–293.CrossRefPubMedGoogle Scholar
  21. 21.
    Green, S. K., Francia, G., Isidoro, C., and Kerbel, R. S. (2004) Antiadhesive antibodies targeting E–cadherin sensi–tize multicellular tumor spheroids to chemotherapy in vitro, Mol. Cancer Ther., 3, 149–159.PubMedGoogle Scholar
  22. 22.
    Petrova, Y. I., Schecterson, L., and Gumbiner, B. M. (2016) Roles for E–cadherin cell surface regulation in can–cer, Mol. Biol. Cell, 27, 3233–3244.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Chao, Y., Wu, Q., Shepard, C., and Wells, A. (2012) Hepatocyte induced re–expression of E–cadherin in breast and prostate cancer cells increases chemoresistance, Clin. Exp. Metastasis, 29, 39–50.CrossRefPubMedGoogle Scholar
  24. 24.
    Wells, A., and Ma, B. (2017) Friend turned foe: E–cadherin perversely protects micrometastases, Transl. Androl. Urol., 6, 338–340.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Farmakovskaya, M., Khromova, N., Rybko, V., Dugina, V., Kopnin, B., and Kopnin, P. (2016) E–cadherin repression increases amount of cancer stem cells in human A549 lung adenocarcinoma and stimulates tumor growth, Cell Cycle, 15, 1084–1092.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Veitonmaki, N., Hansson, M., Zhan, F., Sundberg, A., Lofstedt, T., Ljungars, A., Li, Z.–C., Martinsson–Niskanen, T., Zeng, M., Yang, Y., Danielsson, L., Kovacek, M., Lundqvist, A., Martensson, L., Teige, I., Tricot, G., and Frendeus, B. (2013) A human ICAM–1 antibody iso–lated by a function–first approach has potent macrophage–dependent antimyeloma activity in vivo, Cancer Cell, 23, 502–515.CrossRefPubMedGoogle Scholar
  27. 27.
    Hale, M. D., Hayden, J. D., and Grabsch, H. I. (2013) Tumour–microenvironment interactions: role of tumour stroma and proteins produced by cancer–associated fibro–blasts in chemotherapy response, Cell. Oncol., 36, 95–112.CrossRefGoogle Scholar
  28. 28.
    Klemm, F., and Joyce, J. A. (2015) Microenvironmental regulation of therapeutic response in cancer, Trends Cell Biol., 25, 198–213.CrossRefPubMedGoogle Scholar
  29. 29.
    Hanahan, D., and Coussens, L. M. (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment, Cancer Cell, 21, 309–322.CrossRefPubMedGoogle Scholar
  30. 30.
    Berns, A., and Pandolfi, P. P. (2014) Tumor microenviron–ment revisited, EMBO Rep., 15, 458–459.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bissell, M. J., and Hines, W. C. (2011) Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression, Nat. Med., 17, 320–329.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Shain, K. H., and Dalton, W. S. (2001) Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR, Mol. Cancer Ther., 1, 69–78.PubMedGoogle Scholar
  33. 33.
    Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., Reinhart–King, C. A., Margulies, S. S., Dembo, M., Boettiger, D., Hammer, D. A., and Weaver, V. M. (2005) Tensional homeostasis and the malignant phenotype, Cancer Cell, 8, 241–254.CrossRefPubMedGoogle Scholar
  34. 34.
    Marturano–Kruik, A., Villasante, A., Yaeger, K., Ambati, S. R., Chramiec, A., Raimondi, M. T., and Vunjak–Novakovic, G. (2018) Biomechanical regulation of drug sensitivity in an engineered model of human tumor, Biomaterials, 150, 150–161.CrossRefPubMedGoogle Scholar
  35. 35.
    Schrader, J., Gordon–Walker, T. T., Aucott, R. L., van Deemter, M., Quaas, A., Walsh, S., Benten, D., Forbes, S. J., Wells, R. G., and Iredale, J. P. (2011) Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells, Hepatology, 53, 1192–1205.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Shin, J.–W., and Mooney, D. J. (2016) Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias, Proc. Natl. Acad. Sci. USA, 113, 12126–12131.CrossRefPubMedGoogle Scholar
  37. 37.
    Villasante, A., and Vunjak–Novakovic, G. (2015) Tissue–engineered models of human tumors for cancer research, Expert Opin. Drug Discov., 10, 257–268.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Carvalho, M. R., Lima, D., Reis, R. L., Oliveira, J. M., and Correlo, V. M. (2017) Anti–cancer drug validation: the con–tribution of tissue engineered models, Stem Cell Rev. Reports, 13, 347–363.CrossRefGoogle Scholar
  39. 39.
    Northey, J. J., Przybyla, L., and Weaver, V. M. (2017) Tissue force programs cell fate and tumor aggression, Cancer Discov., 7, 1224–1237.CrossRefPubMedGoogle Scholar
  40. 40.
    Bebawy, M., Combes, V., Lee, E., Jaiswal, R., Gong, J., Bonhoure, A., and Grau, G. E. R. (2009) Membrane microparticles mediate transfer of P–glycoprotein to drug sensitive cancer cells, Leukemia, 23, 1643–1649.CrossRefPubMedGoogle Scholar
  41. 41.
    Raposo, G., and Stoorvogel, W. (2013) Extracellular vesi–cles: exosomes, microvesicles, and friends, J. Cell Biol., 200, 373–383.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    van der Pol, E., Boing, A. N., Harrison, P., Sturk, A., and Nieuwland, R. (2012) Classification, functions, and clini–cal relevance of extracellular vesicles, Pharmacol. Rev., 64, 676–705.CrossRefPubMedGoogle Scholar
  43. 43.
    Zaborowski, M. P., Balaj, L., Breakefield, X. O., and Lai, C. P. (2015) Extracellular vesicles: composition, biological relevance, and methods of study, Bioscience, 65, 783–797.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Chevkina, E. M., Shcherbakov, A. M., and Zhuravskaya, A. Yu. (2015) Exosomes and transfer of epigenetic information in cancer cells, Yspekhi Mol. Onkol., 2, 8–20.Google Scholar
  45. 45.
    Munson, P., and Shukla, A. (2015) Exosomes: potential in cancer diagnosis and therapy, Medicines, 2, 310–327.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Roseblade, A., Luk, F., Ung, A., and Bebawy, M. (2015) Targeting microparticle biogenesis: a novel approach to the circumvention of cancer multidrug resistance, Curr. Cancer Drug Targets, 15, 205–214.CrossRefPubMedGoogle Scholar
  47. 47.
    Pokharel, D., Padula, M. P., Lu, J. F., Tacchi, J. L., Luk, F., Djordjevic, S. P., and Bebawy, M. (2014) Proteome analysis of multidrug–resistant, breast cancer–derived microparticles, J. Extracell. Vesicles, 3, 24384.CrossRefGoogle Scholar
  48. 48.
    Johnson, P., and Ruffell, B. (2009) CD44 and its role in inflammation and inflammatory diseases, Inflamm. Allergy Drug Targets, 8, 208–220.CrossRefPubMedGoogle Scholar
  49. 49.
    Miletti–Gonzalez, K. E., Chen, S., Muthukumaran, N., Saglimbeni, G. N., Wu, X., Yang, J., Apolito, K., Shih, W. J., Hait, W. N., and Rodriguez–Rodriguez, L. (2005) The CD44 receptor interacts with P–glycoprotein to promote cell migration and invasion in cancer, Cancer Res., 65, 6660–6667.CrossRefPubMedGoogle Scholar
  50. 50.
    Pokharel, D., Padula, M., Lu, J., Jaiswal, R., Djordjevic, S., and Bebawy, M. (2016) The role of CD44 and ERM proteins in expression and functionality of P–glycoprotein in breast cancer cells, Molecules, 21, 290.CrossRefPubMedGoogle Scholar
  51. 51.
    Stickeler, E., Fraser, S. D., Honig, A., Chen, A. L., Berget, S. M., and Cooper, T. A. (2001) The RNA binding protein YB–1 binds A/C–rich exon enhancers and stimulates splicing of the CD44 alternative exon v4, EMBO J., 20, 3821–3830.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    To, K., Fotovati, A., Reipas, K. M., Law, J. H., Hu, K., Wang, J., Astanehe, A., Davies, A. H., Lee, L., Stratford, A. L., Raouf, A., Johnson, P., Berquin, I. M., Royer, H.–D., Eaves, C. J., and Dunn, S. E. (2010) Y–box binding protein–1 induces the expression of CD44 and CD49f lead–ing to enhanced self–renewal, mammosphere growth, and drug resistance, Cancer Res., 70, 2840–2851.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Dhillon, J., Astanehe, A., Lee, C., Fotovati, A., Hu, K., and Dunn, S. E. (2010) The expression of activated Y–box binding protein–1 serine 102 mediates trastuzumab resist–ance in breast cancer cells by increasing CD44+ cells, Oncogene, 29, 6294–6300.CrossRefPubMedGoogle Scholar
  54. 54.
    Pokharel, D., Roseblade, A., Oenarto, V., Lu, J. F., and Bebawy, M. (2017) Proteins regulating the intercellular transfer and function of P–glycoprotein in multidrug–resist–ant cancer, Ecancermedicalscience, 11, 768.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Stavrovskaya, A. A., and Moiseeva, N. I. (2016) Non–canonic functions of P–glycoprotein transporter, Biol. Membr. (Moscow), 33, 323–334.Google Scholar
  56. 56.
    Smyth, M. J., Krasovskis, E., Sutton, V. R., and Johnstone, R. W. (1998) The drug efflux protein, P–glycoprotein, addi–tionally protects drug–resistant tumor cells from multiple forms of caspase–dependent apoptosis, Proc. Natl. Acad. Sci. USA, 95, 7024–7029.Google Scholar
  57. 57.
    Johnstone, R. W., Cretney, E., and Smyth, M. J. (1999) P–glycoprotein protects leukemia cells against caspase–dependent, but not caspase–independent, cell death, Blood, 93, 1075–1085.PubMedGoogle Scholar
  58. 58.
    Bezombes, C., Maestre, N., Laurent, G., Levade, T., Bettaieb, A., and Jaffrezou, J. P. (1998) Restoration of TNF–alpha–induced ceramide generation and apoptosis in resistant human leukemia KG1a cells by the P–glycoprotein blocker PSC833, FASEB J., 12, 101–109.CrossRefPubMedGoogle Scholar
  59. 59.
    Robinson, L. J., Roberts, W. K., Ling, T. T., Lamming, D., Sternberg, S. S., and Roepe, P. D. (1997) Human MDR 1 protein overexpression delays the apoptotic cascade in Chinese hamster ovary fibroblasts, Biochemistry, 36, 11169–11178.CrossRefPubMedGoogle Scholar
  60. 60.
    Pallis, M., and Russell, N. (2000) P–glycoprotein plays a drug–efflux–independent role in augmenting cell survival in acute myeloblastic leukemia and is associated with modula–tion of a sphingomyelin–ceramide apoptotic pathway, Blood, 95, 2897–2904.PubMedGoogle Scholar
  61. 61.
    Pallis, M., Turzanski, J., Grundy, M., Seedhouse, C., and Russell, N. (2003) Resistance to spontaneous apoptosis in acute myeloid leukaemia blasts is associated with P–glyco–protein expression and function, but not with the presence of FLT3 internal tandem duplications, Br. J. Haematol., 120, 1009–1016.CrossRefPubMedGoogle Scholar
  62. 62.
    Tainton, K. M., Smyth, M. J., Jackson, J. T., Tanner, J. E., Cerruti, L., Jane, S. M., Darcy, P. K., and Johnstone, R. W. (2004) Mutational analysis of P–glycoprotein: suppression of caspase activation in the absence of ATP–dependent drug efflux, Cell Death Differ., 11, 1028–1037.CrossRefPubMedGoogle Scholar
  63. 63.
    Souza, P. S., Madigan, J. P., Gillet, J.–P., Kapoor, K., Ambudkar, S. V., Maia, R. C., Gottesman, M. M., and Fung, K. L. (2015) Expression of the multidrug transporter P–glycoprotein is inversely related to that of apoptosis–associated endogenous TRAIL, Exp. Cell Res., 336, 318–328.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., and Smith, C. A. (1995) Identification and characterization of a new member of the TNF family that induces apoptosis, Immunity, 3, 673–682.CrossRefPubMedGoogle Scholar
  65. 65.
    Kano, T., Wada, S., Morimoto, K., Kato, Y., and Ogihara, T. (2011) Effect of knockdown of ezrin, radixin, and moesin on P–glycoprotein function in HepG2 cells, J. Pharm. Sci., 100, 5308–5314.CrossRefPubMedGoogle Scholar
  66. 66.
    Zhang, L., Xiao, R., Xiong, J., Leng, J., Ehtisham, A., Hu, Y., Ding, Q., Xu, H., Liu, S., Wang, J., Tang, D. G., and Zhang, Q. (2013) Activated ERM protein plays a critical role in drug resistance of MOLT4 cells induced by CCL25, PLoS One, 8, e52384.Google Scholar
  67. 67.
    Wang, W.–J., Li, Q.–Q., Xu, J.–D., Cao, X.–X., Li, H.–X., Tang, F., Chen, Q., Yang, J.–M., Xu, Z.–D., and Liu, X.–P. (2008) Interaction between CD147 and P–glycoprotein and their regulation by ubiquitination in breast cancer cells, Chemotherapy, 54, 291–301.CrossRefPubMedGoogle Scholar
  68. 68.
    Li, Q.–Q., Wang, W.–J., Xu, J.–D., Cao, X.–X., Chen, Q., Yang, J.–M., and Xu, Z.–D. (2007) Involvement of CD147 in regulation of multidrug resistance to P–gp substrate drugs and in vitro invasion in breast cancer cells, Cancer Sci., 98, 1064–1069.CrossRefPubMedGoogle Scholar
  69. 69.
    Jodoin, J., Demeule, M., Fenart, L., Cecchelli, R., Farmer, S., Linton, K. J., Higgins, C. F., and Beliveau, R. (2003) P–glycoprotein in blood–brain barrier endothelial cells: interaction and oligomerization with caveolins, J. Neurochem., 87, 1010–1023.CrossRefPubMedGoogle Scholar
  70. 70.
    Belanger, M. M., Gaudreau, M., Roussel, E., and Couet, J. (2004) Role of caveolin–1 in etoposide resistance develop–ment in A549 lung cancer cells, Cancer Biol. Ther., 3, 954–959.CrossRefPubMedGoogle Scholar
  71. 71.
    Barakat, S., Demeule, M., Pilorget, A., Regina, A., Gingras, D., Baggetto, L. G., and Beliveau, R. (2006) Modulation of P–glycoprotein function by caveolin–1 phos–phorylation, J. Neurochem., 101, 1–8.CrossRefGoogle Scholar
  72. 72.
    Bhuin, T., and Roy, J. K. (2014) Rab proteins: the key reg–ulators of intracellular vesicle transport, Exp. Cell Res., 328, 1–19.CrossRefPubMedGoogle Scholar
  73. 73.
    Liu, M., Aneja, R., Wang, H., Sun, L., Dong, X., Huo, L., Joshi, H., and Zhou, J. (2007) Modulation of multidrug resistance in cancer cells by the E3 ubiquitin ligase seven–in–absentia homologue 1, J. Pathol., 214, 508–514.CrossRefGoogle Scholar
  74. 74.
    Kim, H.–B., Lee, S.–H., Um, J.–H., Kim, M.–J., Hyun, S.–K., Gong, E.–J., Oh, W. K., Kang, C.–D., and Kim, S.–H. (2015) Sensitization of chemo–resistant human chronic myeloid leukemia stem–like cells to Hsp90 inhibitor by SIRT1 inhibition, Int. J. Biol. Sci., 11, 923–934.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Xin, Y., Yin, F., Qi, S., Shen, L., Xu, Y., Luo, L., Lan, L., and Yin, Z. (2013) Parthenolide reverses doxorubicin resistance in human lung carcinoma A549 cells by attenu–ating NF–αB activation and HSP70 up–regulation, Toxicol. Lett., 221, 73–82.CrossRefPubMedGoogle Scholar
  76. 76.
    Sutoh, I., Kohno, H., Nakashima, Y., Hishikawa, Y., Tabara, H., Tachibana, M., Kubota, H., and Nagasue, N. (2000) Concurrent expressions of metallothionein, glu–tathione S–transferase–pi, and P–glycoprotein in colorectal cancers, Dis. Colon Rectum, 43, 221–232.CrossRefPubMedGoogle Scholar
  77. 77.
    Tsuda, H., Hirohashi, S., Shimosato, Y., Hirota, T., Tsugane, S., Yamamoto, H., Miyajima, N., Toyoshima, K., Yamamoto, T., and Yokota, J. (1989) Correlation between long–term survival in breast cancer patients and amplifica–tion of two putative oncogene–coamplification units: hst–1/int–2 and c–erbB–2/ear–1, Cancer Res., 49, 3104–3108.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Blokhin Medical Research Center of OncologyMinistry of Health of the Russian FederationMoscowRussia

Personalised recommendations