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PMID: 3459187 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Isolation of human mdr DNA sequences amplified in multidrug-resistant KB carcinoma cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 12 ·1986-06-00 ·Pages 4538-42

Roninson IB, Chin JE, Choi KG, Gros P, Housman DE, Fojo A, Shen DW, Gottesman MM, Pastan I

Abstract

The ability of tumor cells to develop simultaneous resistance to structurally different cytotoxic drugs constitutes a major problem in cancer chemotherapy. It was previously demonstrated that multidrug-resistant Chinese hamster cell lines contain an amplified, transcriptionally active DNA sequence designated mdr. This report presents evidence that multidrug-resistant sublines of human KB carcinoma cells, selected for resistance to either colchicine, vinblastine, or Adriamycin (doxorubicin), display amplification of two different DNA sequences homologous to the hamster mdr gene. Segments of the human mdr DNA sequences, designated mdr1 and mdr2, have been cloned. mdr1 sequences were amplified in all of the highly drug-resistant sublines and were expressed as a poly(A)+ RNA species of 4.5 kilobases that was detected in the resistant cells but not in the parental cell line. No expression of mdr2 sequences was detected. mdr2 sequences were coamplified with mdr1 in some of the multidrug-resistant sublines and, in two independently derived cell lines, underwent very similar rearrangements. The data suggest that the mdr1 gene is involved in multidrug resistance in human cells.

MeSH Terms
Carcinoma/genetics Cloning, Molecular Colchicine/pharmacology DNA, Neoplasm/genetics Doxorubicin/pharmacology Drug Resistance Gene Amplification Humans KB Cells/drug effects Nucleic Acid Hybridization Recombination, Genetic Vinblastine/pharmacology
Chemicals
DNA, Neoplasm Vinblastine Doxorubicin Colchicine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Roninson I B
Chin J E
Choi K G
Gros P
Housman D E
Fojo A
Shen D W
Gottesman M M
Pastan I
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.83.12.4538
Published
1986-06-00
Pages
4538-42
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323769
Subset
IM
Grants
NCI NIH HHS · CA40333 · United States
External Links
PubMed source DOI: 10.1073/pnas.83.12.4538 PMC Full Text View journal details
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