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

Journal Article · Fri May 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.9.3004· OSTI ID:5964645

Ueda, K; Cardarelli, C; Gottesman, M M; Pastan, I

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 (NIH), Bethesda, MD (United States)
• OSTI ID: 5964645
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:9
• Country of Publication: United States
• Language: English

Related Subjects

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