Resistance to the nucleotide analogue cidofovir in HPV(+) cells: a multifactorial process involving UMP/CMP kinase 1
| Autor: | Tim De Schutter, Marcela Krečmerová, Lieve Naesens, Graciela Andrei, Dimitrios Topalis, Robert Snoeck, Tatiane C Nogueira, Chahrazade El Amri, Jan Balzarini |
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| Přispěvatelé: | Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB / CAS), Czech Academy of Sciences [Prague] (CAS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rega Institute for Medical Research, Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences [Prague] (ASCR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
UMP-CMP kinase viruses Uterine Cervical Neoplasms Uridine Triphosphate chemistry.chemical_compound 0302 clinical medicine Papillomaviridae Phosphorylation human papillomavirus Uridine triphosphate Cervical cancer Nucleoside-phosphate kinase biology Multidrug resistance-associated protein 2 virus diseases 3. Good health Oncology 030220 oncology & carcinogenesis Female cervical carcinoma Cytosine Cidofovir Research Paper Cytidine Triphosphate Organophosphonates [SDV.CAN]Life Sciences [q-bio]/Cancer Microbial Sensitivity Tests [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics cidofovir 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Cell Line Tumor medicine Humans NTP metabolism Solute Carrier Proteins Papillomavirus Infections Transporter medicine.disease biology.organism_classification Virology [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics 030104 developmental biology chemistry Drug Resistance Neoplasm Cancer research ATP-Binding Cassette Transporters Nucleoside-Phosphate Kinase HeLa Cells |
| Zdroj: | Oncotarget Oncotarget, Impact journals, 2016, 7 (9), pp.10386-10401. ⟨10.18632/oncotarget.7006⟩ Oncotarget, 2016, 7 (9), pp.10386-10401. ⟨10.18632/oncotarget.7006⟩ |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.7006⟩ |
| Popis: | Human papillomavirus (HPV) is responsible for cervical cancer, and its role in head and neck carcinoma has been reported. No drug is approved for the treatment of HPV-related diseases but cidofovir (CDV) exhibits selective antiproliferative activity.In this study, we analyzed the effects of CDV-resistance (CDVR) in two HPV(+) (SiHaCDV and HeLaCDV) and one HPV(-) (HaCaTCDV) tumor cell lines. Quantification of CDV metabolites and analysis of the sensitivity profile to chemotherapeutics was performed. Transporters expression related to multidrug-resistance (MRP2, P-gp, BCRP) was also investigated.Alterations of CDV metabolism in SiHaCDV and HeLaCDV, but not in HaCaTCDV, emerged via impairment of UMP/CMPK1 activity. Mutations (P64T and R134M) as well as down-regulation of UMP/CMPK1 expression were observed in SiHaCDV and HeLaCDV, respectively. Altered transporters expression in SiHaCDV and/or HeLaCDV, but not in HaCaTCDV, was also noted.Taken together, these results indicate that CDVR in HPV(+) tumor cells is a multifactorial process. ispartof: Oncotarget vol:7 issue:9 pages:10386-10401 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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