title: Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.
abstract: Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2μM cells and MES-SA/DxR-8μM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Eugenie Wong Soon
authors.initials: EW
authors.lastname: May
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Szu-Ting
authors.initials: ST
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan; Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taiwan; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Jo-Fan
authors.initials: JF
authors.lastname: Chang
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Eric
authors.initials: E
authors.lastname: Hung
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lo
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Li-Hsun
authors.initials: LH
authors.lastname: Lin
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ren-Yu
authors.initials: RY
authors.lastname: Hu
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Chi-Lun
authors.initials: CL
authors.lastname: Feng
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Dai-Ying
authors.initials: DY
authors.lastname: Lin
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Shine-Bei
authors.initials: SB
authors.lastname: Wu
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Lee
authors.affiliation: Lutheran Medical Center, Brooklyn, NY, USA; Global Scholars Program, St. George's University/Northumbria University, Newcastle upon Tyne, United Kingdom.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Lyu
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan. Electronic address: hlchan@life.nthu.edu.tw.
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Chou
authors.affiliation: Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan. Electronic address: chouhc@mail.nhcue.edu.tw.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D020543:Proteome; D034741:RNA, Small Interfering / Q000008:administration & dosage; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation / Q000187:drug effects; D014594:Uterine Neoplasms / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D002135:Calcium-Binding Proteins; D020543:Proteome; C000597745:RCN1 protein, human; D034741:RNA, Small Interfering; D004317:Doxorubicin
keywords: DIGE; Doxorubicin; Resistance; Reticulocalbin-1; Uterine cancer