Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction

K. E. Noonan, C. Beck, T. A. Holzmayer, J. E. Chin, J. S. Wunder, I. L. Andrulis, A. F. Gazdar, C. L. Willman, B. Griffith, D. D. Von Hoff, I. B. Roninson

Research output: Contribution to journalArticle

754 Citations (Scopus)

Abstract

The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refractory tumors untreated with chemotherapeutic drugs. We have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clinical samples, based on the polymerase chain reaction. We have used this assay to measure MDR1 gene expression in MDR cell lines and >300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expression were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of samples without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were most common among tumor types known to be relatively responsive to chemotherapy.

Original languageEnglish (US)
Pages (from-to)7160-7164
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number18
StatePublished - Sep 1990

Fingerprint

MDR Genes
Gene Expression
Polymerase Chain Reaction
Neoplasms
P-Glycoprotein
Drug Resistance
Drug Therapy
Cell Line
Messenger RNA
Multiple Drug Resistance
Tumor Cell Line
Pharmaceutical Preparations
Limit of Detection
Leukemia

Keywords

  • β-microglobulin
  • Leukemias
  • P-glycoprotein
  • RNA measurement
  • Solid tumors

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Noonan, K. E., Beck, C., Holzmayer, T. A., Chin, J. E., Wunder, J. S., Andrulis, I. L., ... Roninson, I. B. (1990). Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America, 87(18), 7160-7164.

Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. / Noonan, K. E.; Beck, C.; Holzmayer, T. A.; Chin, J. E.; Wunder, J. S.; Andrulis, I. L.; Gazdar, A. F.; Willman, C. L.; Griffith, B.; Von Hoff, D. D.; Roninson, I. B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 18, 09.1990, p. 7160-7164.

Research output: Contribution to journalArticle

Noonan, KE, Beck, C, Holzmayer, TA, Chin, JE, Wunder, JS, Andrulis, IL, Gazdar, AF, Willman, CL, Griffith, B, Von Hoff, DD & Roninson, IB 1990, 'Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction', Proceedings of the National Academy of Sciences of the United States of America, vol. 87, no. 18, pp. 7160-7164.
Noonan, K. E. ; Beck, C. ; Holzmayer, T. A. ; Chin, J. E. ; Wunder, J. S. ; Andrulis, I. L. ; Gazdar, A. F. ; Willman, C. L. ; Griffith, B. ; Von Hoff, D. D. ; Roninson, I. B. / Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. In: Proceedings of the National Academy of Sciences of the United States of America. 1990 ; Vol. 87, No. 18. pp. 7160-7164.
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