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Expression of a full-length cDNA for the human MDR1 gene confers resistance to colchicine, doxorubicin, and vinblastine

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
; ; ;
Intrinsic and acquired multidrug resistance (MDR) is an important problem in cancer therapy. MDR in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or doxorubicin (former generic name adriamycin) is associated with overexpression of the MDR1 gene, which encodes P-glycoprotein. The authors previously have isolated an overlapping set of cDNA clones for the human MDR1 gene from multidrug-resistant KB cells. Here they report the construction of a full-length cDNA for the human MDR1 gene and show that this reconstructed cDNA, when inserted into a retroviral expression vector containing the long terminal repeats of Moloney leukemia virus or Harvey sarcoma virus, functions in mouse NIH 3T3 and human KB cells to confer the complete multidrug-resistance phenotype. These results suggest that the human MDR1 gene may be used as a positive selectable marker to introduce genes into human cells and to transform human cells to multidrug resistance without introducing nonhuman antigens.
Research Organization:
National Institutes of Health, Bethesda, MD
OSTI ID:
5964645
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:9; ISSN PNASA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALOIDS
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
ANTIPYRETICS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARCINOMAS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMOTHERAPY
COLCHICINE
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DOXORUBICIN
DRUGS
ENZYMES
ESTERASES
GENES
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
HYDROLASES
INDOLES
ISOTOPES
LIGHT NUCLEI
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHODIESTERASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PYRROLES
RADIOISOTOPES
RECOMBINANT DNA
RNA-ASE
SENSITIVITY
THERAPY
TUMOR CELLS
VINBLASTINE