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Multidrug-resistant cancer cells facilitate E1-independent adenoviral replication: Impact for cancer gene therapy

Item Type:Article
Title:Multidrug-resistant cancer cells facilitate E1-independent adenoviral replication: Impact for cancer gene therapy
Creators Name:Holm, P.S. and Lage, H. and Bergmann, S. and Juerchott, K. and Glockzin, G. and Bernshausen, A. and Mantwill, K. and Ladhoff, A. and Wichert, A. and Mymryk, J.S. and Ritter, T. and Dietel, M. and Gaensbacher, B. and Royer, H.D.
Abstract:Resistance to chemotherapy is responsible for a failure of current treatment regimens in cancer patients. We have reported previously that the Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major role in the development of a multidrug resistant-tumor phenotype. YB-1 predicts drug resistance and patient outcome in breast cancer. Thus, YB-1 is a promising target for new therapeutic approaches to defeat multidrug resistance. In drug-resistant cancer cells and in adenovirus-infected cells YB-1 is found in the nucleus. Nuclear accumulation of YB-1 in adenovirus-infected cells is a function of the El region, and we have shown that YB-1 facilitates adenovirus replication. Here we report that E1A-deleted or mutant adenovirus vectors, such as Ad312 and Ad520, replicate efficiently in multidrug-resistant (MDR) cancer cells and induce an adenovirus cytopathic effect resulting in host cell lysis. Thus, replication-defective adenoviruses are a previously unrecognized vector system for a selective elimination of MDR cancer cells. Our work forms the basis for the development of novel oncolytic adenovirus vectors for the treatment of MDR malignant diseases in the clinical setting.
Keywords:Adenovirus E1A Proteins, Base Sequence, Cell Line, Complementary DNA, DNA Primers, Gene Deletion, Gene Therapy, Hela Cells, Human Adenoviruses, Multiple Drug Resistance, Neoplasms, Transfection, Tumor Cell Line, Virus Replication
Source:Cancer Research
Publisher:American Association for Cancer Research
Page Range:322-328
Date:1 January 2004
Official Publication:https://doi.org/10.1158/0008-5472.CAN-0482-2
PubMed:View item in PubMed

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