Title |
MSH2 Dysregulation Is Triggered by Proinflammatory Cytokine Stimulation and Is Associated with Liver Cancer Development
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Published in |
Cancer Research, July 2016
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DOI | 10.1158/0008-5472.can-15-2926 |
Pubmed ID | |
Authors |
Yuji Eso, Atsushi Takai, Tomonori Matsumoto, Tadashi Inuzuka, Takahiro Horie, Koh Ono, Shinji Uemoto, Kyeryoung Lee, Winfried Edelmann, Tsutomu Chiba, Hiroyuki Marusawa |
Abstract |
Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here we demonstrated that TNF-α stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via nuclear factor-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2-/-AID+, ALB-MSH2-/-, and ALB-AID+ mice in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2-/-AID+ mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 29% |
Researcher | 7 | 25% |
Other | 2 | 7% |
Student > Bachelor | 1 | 4% |
Professor | 1 | 4% |
Other | 4 | 14% |
Unknown | 5 | 18% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 9 | 32% |
Biochemistry, Genetics and Molecular Biology | 4 | 14% |
Agricultural and Biological Sciences | 3 | 11% |
Immunology and Microbiology | 2 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 2 | 7% |
Unknown | 7 | 25% |