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

Journal Article · Sat Sep 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.18.7160· OSTI ID:5272377

Noonan, K E; Beck, C; Holzmayer, T A; Chin, J E; Roninson, I B ^[1]; Wunder, J S; Andrulis, I L ^[2]; Gazdar, A F ^[3]; Willman, C L; Griffith, B ^[4]; Von Hoff, D D ^[5]

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1. Univ. of Illinois, Chicago (USA)
2. Mount Sinai Hospital, Toronto, Ontario (Canada)
3. National Cancer Inst., Bethesda, MD (USA)
4. Univ. of New Mexico, Albuquerque (USA)
5. Univ. of Texas, San Antonio (USA)

The resistance of tumor cells ot chemotheraprutic 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 bitro 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 refactory tumors untreated with chemotherapeutic drugs. The authors have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clincal samples, based on the polymerase chain reaction. They 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 ost common among tumor types known to be relatively responsive to chemotherapy.

• OSTI ID: 5272377
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:18; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
CHEMISTRY
CHEMOTHERAPY
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DRUGS
ENZYMES
GENE AMPLIFICATION
GENE REGULATION
IMMUNE SYSTEM DISEASES
ISOTOPES
LEUKEMIA
LIGHT NUCLEI
MAMMALS
MAN
MESSENGER-RNA
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PRIMATES
RADIOISOTOPES
RECOMBINANT DNA
RNA
RNA POLYMERASES
SENSITIVITY
THERAPY
TRANSFERASES
TUMOR CELLS
VERTEBRATES