Molecular and Cellular Biology of Multidrug Resistance in Tumor Cells

1. Front Matter

   Pages i-xviii

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2. Isolation and Properties of Multidrug-Resistant Cell Lines

   1. Front Matter

      Pages 1-1

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   2. Characteristics of Multidrug Resistance in Human Tumor Cells

      • William T. Beck, Mary K. Danks

      Pages 3-55

   3. Development of Multidrug Resistance in Rodent Cell Lines

      • Yoshikazu Sugimoto, Takashi Tsuruo

      Pages 57-70

3. Molecular Genetics of Multidrug Resistance

   1. Front Matter

      Pages 71-71

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   2. Cloning and Characterization of Mouse mdr Genes

      • Philippe Gros, Martine Raymond, David Housman

      Pages 73-89

   3. Isolation and Characterization of the Human MDR (P-Glycoprotein) Genes

      • Igor B. Roninson, Ira Pastan, Michael M. Gottesman

      Pages 91-106

   4. Amplification of Several Different Genes in Multidrug-Resistant Chinese Hamster Cell Lines

      • P. Borst, A. M. Van Der Bliek

      Pages 107-116

   5. Molecular and Cytogenetic Analysis of Multidrug Resistance-Associated Gene Amplification in Chinese Hamster, Mouse Sarcoma, and Human Neuroblastoma Cells

      • Peter W. Melera, June L. Biedler

      Pages 117-145

   6. Karyotype and Amplicon Evolution during Stepwise Development of Multidrug Resistance in Djungarian Hamster Cell Lines

      • A. V. Gudkov, O. B. Chernova, B. P. Kopnin

      Pages 147-168

   7. Chromosome Localization of P-Glycoprotein Genes in Drug-Sensitive and -Resistant Human Cells

      • Jeffrey M. Trent, David F. Callen

      Pages 169-188

   8. Structure and Evolution of P-Glycoproteins

      • Igor B. Roninson

      Pages 189-211

4. Biochemical Analysis of Multidrug Resistance

   1. Front Matter

      Pages 213-213

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   2. Drug Accumulation and Binding in P-Glycoprotein-Associated Multidrug Resistance

      • William T. Beck

      Pages 215-227

   3. Binding of Drugs and ATP by P-Glycoprotein and Transport of Drugs by Vesicles from Human Multidrug-Resistant Cells

      • Marilyn M. Cornwell, Ira Pastan, Michael M. Gottesman

      Pages 229-242

   4. Protein Changes in Multidrug-Resistant Cells

      • Marian B. Meyers, June L. Biedler

      Pages 243-261

   5. Membrane Lipids of Multidrug-Resistant Cells: Chemical Composition and Physical State

      • Noa Alon, Roger Busche, Burkhard Tümmler, John R. Riordan

      Pages 263-276

5. P-Glycoprotein Expression in Normal and Tumor Tissues

   1. Front Matter

      Pages 277-277

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   2. Expression of the MDR1 Gene in Normal Human Tissues

      • Michael M. Gottesman, Mark C. Willingham, Franz Thiebaut, Ira Pastan

      Pages 279-289

   3. Expression of the Multidrug Resistance Gene in Human Cancer

      • Michael M. Gottesman, Lori J. Goldstein, Antonio Fojo, Hanan Galski, Ira Pastan

      Pages 291-301

The ability of neoplastic cells to survive exposure to various chemotherapeutic drugs represents the main obstacle to successful cancer chemotherapy. This book deals with a particular type of resistance in tumor cells that represents a single but especially important aspect of the multifaceted problem of cancer drug resistance. This type of resistance, known as multidrug or pleiotropic drug resistance, is characterized by cross-resistance of cells to several different classes of cytotoxic drugs, including some of the most commonly used anticancer agents. Over the last several years, there has been a veritable explosion of genetic, biochemical, and clinical information on multidrug resistance, which followed the identification and cloning of the genes responsible for this phenotype and the isolation of monoclonal antibodies against P-glycoproteins, the products of these genes. Elucida­ tion of the molecular mechanism of multidrug resistance has led to the formulation of novel approaches to the prediction of tumor response to chemotherapeutic drugs and increasing the efficacy of cancer therapy. Analysis of the structure and function of P­ glycoproteins from multidrug-resistant mammalian cells has also established a prototype for a novel class of eukaryotic membrane proteins, which have now been associated with a variety of transport processes in different organisms. This book summarizes the results of molecular biological, pharmacological, bio­ chemical, cytogenetic, immunological, and pathological studies on multidrug resistance in mammalian cells. Most of the chapters deal at least to some extent with the structure and expression of P-glycoprotein and its role in multidrug resistance.

• Mammalia
• biology
• cancer
• cancer therapy
• chemotherapy
• drug
• drug resistance
• phenotype
• proteins
• resistance
• tumor
• antibacterial drug resistance

• Department of Genetics, University of Illinois at Chicago, Chicago, USA

  Igor B. Roninson

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