Proteomic analysis of the proteins that are associated with the resistance to paclitaxel in human breast cancer cells

• Published in: Molecular bioSystems Vol. 1; no. 2; pp. 294 - 33
• Main Authors: Chen, Siying, Dong, Qian, Hu, Sasa, Cai, Jiangxia, Zhang, Weipeng, Sun, Jinyao, Wang, Taotao, Xie, Jiao, He, Hairong, Xing, Jianfeng, Lu, Jun, Dong, Yalin
• Format: Journal Article
• Language: English
• Published: England 01.02.2014
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Aspartate Aminotransferases - genetics; Aspartate Aminotransferases - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; DNA-Binding Proteins; Drug Resistance, Neoplasm - genetics; Electrophoresis, Gel, Two-Dimensional; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Heterogeneous-Nuclear Ribonucleoproteins - genetics; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; Histone Chaperones - genetics; Histone Chaperones - metabolism; Humans; MCF-7 Cells; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Muscle Proteins - genetics; Muscle Proteins - metabolism; Nucleoside-Diphosphate Kinase - genetics; Nucleoside-Diphosphate Kinase - metabolism; Paclitaxel - pharmacology; Proteomics - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1742-206X; 1742-2051
• DOI: 10.1039/c3mb70428a

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. Cancers frequently develop resistance to paclitaxel but the underlying molecular mechanisms remain to be determined.