title: Functional roles of glycogene and N-glycan in multidrug resistance of human breast cancer cells.
abstract: Drug resistance is a major problem in cancer chemotherapy. Aberrant glycosylation has been known to be associated with cancer chemoresistance. Aim of this work is to investigate the alterations of glycogene and N-glycan involved in multidrug resistance (MDR) in human breast cancer cell lines. Using real-time polymerase chain reaction (PCR) for quantification of glycogenes, fluorescein isothiocyanate (FITC)-lectin binding for glycan profiling, and mass spectrometry for N-glycan composition, the expression of glycogenes, glycan profiling, and N-glycan composition differed between drug-resistant MCF/ADR cells and the parental MCF-7 line. Further analysis of the N-glycan regulation by tunicamycin (TM) application or PNGase F treatment in MCF/ADR cells showed partial inhibition of the N-glycan biosynthesis and increased sensitivity to chemotherapeutic drugs dramatically both in vitro and in vivo. Using an RNA interference strategy, we showed that the downregulation of MGAT5 in MCF/ADR cells could enhance the chemosensitivity to antitumor drugs both in vitro and in vivo. Conversely, a stable high expression of MGAT5 in MCF-7 cells could increase resistance to chemotherapeutic drugs both in vitro and in vivo. In conclusion, the alterations of glycogene and N-glycan in human breast cancer cells correlate with tumor sensitivity to chemotherapeutic drug and have significant implications for the development of new treatment strategies. © 2013 IUBMB Life, 65(5):409-422, 2013.
authors: College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Hongye
authors: H
authors: Ma
authors: Xiaoyan
authors: X
authors: Miao
authors: Qiuhong
authors: Q
authors: Ma
authors: Wenzhi
authors: W
authors: Zheng
authors: Huimin
authors: H
authors: Zhou
authors: Li
authors: L
authors: Jia
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000503:physiopathology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D061986:MCF-7 Cells; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D011134:Polysaccharides; C479741:MGAT5B protein, human; D017351:N-Acetylglucosaminyltransferases