Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/4311
Title: Identification of doxorubicin drug resistance mechanisms by using genomic techniques
Other Titles: Doksorubisin dirençlilik mekanizmalarının genomik yöntemlerle tespit edilmesi
Authors: Koç, Ahmet
Demir, Ayşe Banu
Keywords: Doxorubicin
Cancer drug resistance
Saccharomyces cerevisiae
Issue Date: Jan-2015
Publisher: Izmir Institute of Technology
Source: Demir, A. B. (2015). Identification of doxorubicin drug resistance mechanisms by using genomic techniques. Unpublished doctoral dissertation, İzmir Institute of Technology, İzmir, Turkey
Abstract: Chemotherapy has been an important contributor for the treatment of cancer patients for a long time. The effectiveness of the therapies is influenced from the toxicity effects of the agents on normal cells and from the drug resistance. Therapeutic resistance is believed to cause the failure of the chemotherapy effectiveness in most cancer cases. Therefore, understanding the molecular mechanisms that underlie the drug resistance may contribute to increase the effectiveness of the chemotherapeutic treatment of cancer. Doxorubicin is a natural product that is widely used in treatment of various cancer types, yet many tumors have resistance against these agents. By using the budding yeast Saccharomyces cerevisiae as a model organism, we performed genome-wide screenings to identify the genes that cause resistance against this agent. Overexpression of CUE5, AKL1, CAN1, YHR177W and PDR5 genes have been identified to cause resistance against Doxorubicin at higher concentrations than the identified toxic level. Among these genes, only PDR5 overexpression was found to have cross-resistance to Cisplatin. Real-time PCR and microarray analysis for these genes were also performed. Upon 80μM Doxorubicin treatment for 2 hours, none of the CUE5, AKL1, CAN1, YHR177W and PDR5 genes showed expression changes compared to their correponding untreated wild-type status. Therefore, overexpression of these genes may not be a physiological response of yeast cells against Doxorubicin. Genome-wide microarray analysis showed changes in several cellular and biological functions upon Doxorubicin treatment. Identified genes mainly function in general stress response related events such as, filamentous growth, protein ubiquitination, autophagy, changes in membrane transportation and metabolic processes.
Description: Thesis (Doctoral)--Izmir Institute of Technology, Molecular Biology and Genetics, Izmir, 2015
Full text release delayed at author's request until 2016.02.03
Includes bibliographical references (leaves: 71-74)
Text in English; Abstract: Turkish and English
x, 77 leaves
URI: http://hdl.handle.net/11147/4311
Appears in Collections:Phd Degree / Doktora

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