title: Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis.
abstract: Chemoresistance is a poor prognostic factor in breast cancer and is a major obstacle to the successful treatment of patients receiving chemotherapy. However, the precise mechanism of resistance remains unclear. In this study, a pair of breast cancer cell lines, MCF-7 and its adriamycin-resistant counterpart MCF-7/ADR was used to examine resistance-dependent cellular responses and to identify potential therapeutic targets. We applied nanoflow liquid chromatography (nLC) and tandem mass tags (TmT) quantitative mass spectrometry to distinguish the differentially expressed proteins (DEPs) between the two cell lines. Bioinformatics analyses were used to identify functionally active proteins and networks. 80 DEPs were identified with either up- or down-regulation. Basing on the human protein-protein interactions (PPI), we have retrieved the associated functional interaction networks for the DEPs and analyzed the biological functions. Six different signaling pathways and most of the DEPs strongly linked to chemoresistance, invasion, metastasis development, proliferation, and apoptosis. The identified proteins in biological networks served to resistant drug and to select critical candidates for validation analyses by western blot. The glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl cyclotransferase (GGCT), isocitrate dehydrogenase 1 (NADP+,soluble)(IDH1), isocitrate dehydrogenase 2 (NADP+,mitochondrial) (IDH2) and glutathione S-transferase pi 1(GSTP1), five of the critical components of GSH pathway, contribute to chemoresistance.
authors.affiliation: 1] Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China [2] Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lian
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin. 150081, Heilongjiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Qijia
authors.initials: Q
authors.lastname: Xuan
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Tieying
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Yanchen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Cancer Research Institute Harbin Medial University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D005722:gamma-Glutamylcyclotransferase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C572776:GGCT protein, human; D004317:Doxorubicin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D005954:Glucosephosphate Dehydrogenase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005722:gamma-Glutamylcyclotransferase
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