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. 1997 Apr 15;99(8):1947-57.
doi: 10.1172/JCI119362.

Gene rearrangement: a novel mechanism for MDR-1 gene activation

L A Mickley  1 , B A Spengler, T A Knutsen, J L Biedler, T Fojo
Affiliations

Gene rearrangement: a novel mechanism for MDR-1 gene activation

L A Mickley et al. J Clin Invest. .

Abstract

Drug resistance, a major obstacle to cancer chemotherapy, can be mediated by MDR-1/P-glycoprotein. Deletion of the first 68 residues of MDR-1 in an adriamycin-selected cell line after a 4;7 translocation, t(4q;7q), resulted in a hybrid mRNA containing sequences from both MDR-1 and a novel chromosome 4 gene. Further selection resulted in amplification of a hybrid gene. Expression of the hybrid mRNA was controlled by the chromosome 4 gene, providing a model for overexpression of MDR-1. Additional hybrid mRNAs in other drug-selected cell lines and in patients with refractory leukemia, with MDR-1 juxtaposed 3' to an active gene, establishes random chromosomal rearrangements with overexpression of hybrid MDR-1 mRNAs as a mechanism of acquired drug resistance.

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References

    1. Biochim Biophys Acta. 1976 Nov 11;455(1):152-62 - PubMed
    1. Blood. 1996 Mar 15;87(6):2496-505 - PubMed
    1. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7575-9 - PubMed
    1. Science. 1986 May 2;232(4750):643-5 - PubMed
    1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4538-42 - PubMed

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