| The AIB1 oncogene enhances human cholangiocarcinoma growth and chemoresistance by simultaneous activation of Akt and Nrf2 pathways. | |
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MedLine Citation:
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PMID: 22213475 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Transcriptional coactivator amplified in breast cancer 1 (AIB1) plays important roles in the progression of several cancers such as prostate cancer, breast cancer, and hepatoceullar carcinoma. However, its role in Cholangiocarcinoma (CCA), a chemoresistant bile duct carcinoma with a poor prognosis, remains unclear. In this study, we found that AIB1 protein was frequently overexpressed in human CCA specimens and CCA cell lines. Down-regulation of AIB1 induced the G2/M arrest and decreased the expression of mitosis-promoting factors including Cyclin A, Cyclin B and Cdk1 through suppressing the Akt pathway, which resulted in inhibiting CCA cell proliferation. In addition, AIB1 enhanced the chemoresistance of CCA cells at least in part through up-regulating the expression of anti-apoptotic protein Bcl-2. AIB1 regulated the expression of Bcl-2 in CCA cells through activating the Akt pathway as well as suppressing intracellular reactive oxygen species (ROS). AIB1 suppressed ROS by up-regulating antioxindants such as glutathione synthetase and glutathione peroxidase, which are targets of the Nrf2, a critical transcription factor that regulates antioxidants, detoxification enzymes and drug efflux proteins. AIB1 also increased the expression of another two Nrf2 targets ABCC2 and ABCG2 to enhance drug efflux. AIB1 served as an essential coactivator for Nrf2 activation by physically interacting with Nrf2 to enhance its transcriptional activity. CONCLUSION: AIB1 plays an important role in proliferation and chemoresistance of CCA through simultaneous activation of Akt and Nrf2 pathways, suggesting that AIB1 is a potential molecular target for CCA treatment. (HEPATOLOGY 2011.). |
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Authors:
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Qiang Chen; Wenjiao Li; Yunyan Wan; Xiaochun Xia; Qiao Wu; Yanling Chen; Zhide Lai; Chundong Yu; Wengang Li |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-27 |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Hepatobiliary Pancreas and Vessel Surgery, Chenggong Hospital of Xiamen University, Xiamen, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China; The First Affiliated Hospital of Xiamen University, Xiamen, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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