Expression of the MDR1Gene (P-Glycoprotein) in Breast Cancer

  • R. S. Weinstein
  • K. K. Hansen
  • R. B. McBeath
  • W. S. Dalton
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 127)

Abstract

Of the many types of drug resistance reported in the literature, one of the best characterized is classic multidrug resistance, a genetically determined type of resistance to chemotherapy [1,2]. Cancers exhibiting intrinsic multidrug resistance mediated by P-glycoprotein, the product of the MDR1 gene, do not respond to chemotherapy upon primary exposure to “natural product” lipophilic drugs such as colchicine, vinblastine, and doxorubicin. Characteristics of multidrug resistance in cancer cells include: (a) increased levels of P-glycoprotein, a 170-kDa membrane transporter, (b) decreased drug accumulation and enhanced drug efflux, (c) chemoresistance to multiple natural product agents, and (d) chemosensitization by transporter inhibitors (e.g., verapamil). Other cancers that respond initially to drugs may subsequently become resistant to these and other drugs to which the patient has had no previous exposure. This is multidrug resistance in the acquired form. Tumors with either intrinsic or acquired multidrug resistance mediated by P-glycoprotein usually are not cross-resistant to alkylating agents, most antimetabolites, or heavy metals. Often, intrinsic multidrug resistance occurs in tumors derived from organs that normally express P-glycoprotein, such as intestine, liver, kidney, and adrenal [3]. The multidrug resistance phenotype also occurs in the absence of P-glycoprotein, reflecting the multiplicity of mechanisms that produce this phenomenon [4].

Keywords

Permeability Hydrolysis Lymphoma Estrogen Leukemia 

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Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • R. S. Weinstein
    • 1
  • K. K. Hansen
    • 1
  • R. B. McBeath
    • 1
  • W. S. Dalton
    • 1
  1. 1.Departments of Pathology, Surgery, and Internal Medicinethe Arizona Cancer CenterTucsonUSA

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