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The drug resistance-related protein LRP is the human major vault protein

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Abstract

Multidrug-resistant cancer cells frequently overexpress the 110-kD LRP protein (originally named Lung Resistance-related Protein). LRP overexpression has been found to predict a poor response to chemotherapy in acute myeloid leukaemia and ovarian carcinoma. We describe the cloning and chromosome localization of the gene coding for this novel protein. The deduced LRP amino acid sequence shows 87.7% identity with the 104-kD rat major vault protein. Vaults are multi-subunit structures that may be involved in nucleo-cytoplasmic transport. The LRP gene is located on chromosome 16, close to the genes coding for multidrug resistance-associated protein and protein kinase C-β, and may mediate drug resistance, perhaps via a transport process.

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Authors and Affiliations

  1. Department of Pathology, Free University Hospital, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    George L. Scheffer, Marcel J. Flens, Miguel A. Izquierdo, Chris J.L.M. Meijer & Rik J. Scheper

  2. Department of Oncology Free University Hospital, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Herbert M. Pinedo

  3. Department of Immunology, Academic University Hospital, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands

    Peter L.J. Wijngaard & Hans C. Clevers

  4. Department of Cytogenetics, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California, 91010-0269, USA

    Marilyn L. Slovak

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  1. George L. Scheffer
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  2. Peter L.J. Wijngaard
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  3. Marcel J. Flens
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  4. Miguel A. Izquierdo
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  7. Chris J.L.M. Meijer
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  9. Rik J. Scheper
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Scheffer, G., Wijngaard, P., Flens, M. et al. The drug resistance-related protein LRP is the human major vault protein. Nat Med 1, 578–582 (1995). https://doi.org/10.1038/nm0695-578

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