title: High-Copy Overexpression Screening Reveals PDR5 as the Main Doxorubicin Resistance Gene in Yeast.
abstract: Doxorubicin is one of the most potent anticancer drugs used in the treatment of various cancer types. The efficacy of doxorubicin is influenced by the drug resistance mechanisms and its cytotoxicity. In this study, we performed a high-copy screening analysis to find genes that play a role in doxorubicin resistance and found several genes (CUE5, AKL1, CAN1, YHR177W and PDR5) that provide resistance. Among these genes, overexpression of PDR5 provided a remarkable resistance, and deletion of it significantly rendered the tolerance level for the drug. Q-PCR analyses suggested that transcriptional regulation of these genes was not dependent on doxorubicin treatment. Additionally, we profiled the global expression pattern of cells in response to doxorubicin treatment and highlighted the genes and pathways that are important in doxorubicin tolerance/toxicity. Our results suggest that many efflux pumps and DNA metabolism genes are upregulated by the drug and required for doxorubicin tolerance.
authors.affiliation: Izmir Institute of Technology, Department of Molecular Biology and Genetics, Urla, Izmir, Turkey.|Dokuz Eylul University, Institute of Oncology, Department of Basic Oncology, Izmir, Turkey.
authors.forename: Ayse Banu
authors.initials: AB
authors.lastname: Demir
authors.affiliation: Izmir Institute of Technology, Department of Molecular Biology and Genetics, Urla, Izmir, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Koc
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D025141:Drug Resistance, Fungal / Q000502:physiology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; C092438:PDR5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004317:Doxorubicin