title: Abnormal expression of the mitotic checkpoint protein BubR1 contributes             to the anti-microtubule drug resistance of esophageal squamous cell carcinoma             cells.
abstract: Esophageal cancer is a common malignancy with a high mortality rate. The             lack of effective chemotherapy and a means to overcome drug resistance leads to             the predictable failure of esophageal cancer treatment. Mitotic checkpoint proteins             play a critical role in regulating the cell cycle and proliferation. Abnormal             expression of the mitotic checkpoint protein BubR1 has been reported in several             types of cancers. In this study, we investigated the role of BubR1 in conferring             resistance of esophageal cancer cells to anti-microtubule drugs. Using quantitative             real-time PCR analysis on 50 samples of paired esophageal squamous cell cancer             (ESC) tissues and adjacent non-cancerous tissues, we found that 72% (36 of 50)             of the analyzed ESC samples exhibited high expression levels of BubR1, which was             also confirmed in ESC cell lines. ESC cells with high levels of BubR1 were less             sensitive to the anti-microtubule drugs paclitaxel and nocodazole. Recombinant             adenovirus-mediated enforced expression of BubR1 in relatively sensitive ESC cell             lines resulted in increased resistance to paclitaxel. Conversely, RNAi-mediated             knockdown of BubR1 restored ESC cell sensitivity to paclitaxel. Cell cycle analysis             indicated that the sub-G1 population increased in the ESC cells with reduced BubR1             levels. Taken together, our results suggest that upregulation of BubR1 expression             may be associated with ESC resistance to paclitaxel treatment. Thus, BubR1 may             serve as a potential chemosensitizing target to overcome chemoresistance.
authors.affiliation: Key Laboratory of Diagnostic Medicine designated by The Chinese Ministry of Education and School of Diagnostic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Liu
authors.forename: Peipei
authors.initials: P
authors.lastname: Song
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhan
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Dandan
authors.initials: D
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Fengbing
authors.initials: F
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Guowei
authors.initials: G
authors.lastname: Zuo
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Jinyong
authors.initials: J
authors.lastname: Luo
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Weng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009367:Neoplasm Staging; D015739:Nocodazole / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050257:Tubulin Modulators / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D017239:Paclitaxel; D015739:Nocodazole