title: Proteomic analysis of the proteins that are associated with the resistance to paclitaxel in human breast cancer cells.
abstract: Cancers frequently develop resistance to paclitaxel but the underlying molecular mechanisms remain to be determined. We have investigated the proteins that are associated with the paclitaxel resistance in human breast cancer MCF-7 cells using proteomic analysis. Paclitaxel resistant human breast cancer MCF-7 cells (MCF-7/P) were established by escalating the concentrations of paclitaxel to drug-sensitive MCF-7 cells (MCF-7/S). The global protein profiles of MCF-7/P and MCF-7/S were compared using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Eleven proteins were upregulated while six proteins were downregulated in MCF-7/P cells. Western blot and real-time PCR analyses showed that the protein and mRNA levels of heterogeneous nuclear ribonucleoprotein (hnRNP C1/C2), SET nuclear oncogene (SET), aspartate aminotransferase (AAT), transgelin-2 (TAGLN2) were increased, while those of nucleoside-diphosphate kinase A (NDKA) were decreased in MCF-7/P cells. Accordingly, knockdown of TAGLN2 by siRNA sensitized MCF-7/P cells to paclitaxel and reduced the multidrug resistance (MDR). Our identification of differential proteins, particularly transgelin-2, provides new insights into the mechanism of MDR to paclitaxel and novel biological targets for breast cancer treatment.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. dongyalin@mail.xjtu.edu.cn lujun_2002@aliyun.com.
authors.forename: Siying
authors.initials: S
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Sasa
authors.initials: S
authors.lastname: Hu
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Cai
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Jinyao
authors.initials: J
authors.lastname: Sun
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.forename: Hairong
authors.initials: H
authors.lastname: He
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D056488:Histone Chaperones; D008840:Microfilament Proteins; D009124:Muscle Proteins; C513473:SET protein, human; C585387:Tagln2 protein, human; D014157:Transcription Factors; D001219:Aspartate Aminotransferases; D009701:Nucleoside-Diphosphate Kinase; D017239:Paclitaxel