H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response
Author Manuscript: 2012 April 1.
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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American Association for Cancer Research
2012
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| Online Access: | http://hdl.handle.net/1721.1/75430 https://orcid.org/0000-0001-9307-6116 https://orcid.org/0000-0002-2325-552X |
| _version_ | 1826199398343770112 |
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| author | Garcia, Alexis Zeng, Yu Muthupalani, Sureshkumar Ge, Zhongming Potter, Amanda Mobley, Melissa W. Boussahmain, Chakib Feng, Yan Wishnok, John S. Fox, James G. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Garcia, Alexis Zeng, Yu Muthupalani, Sureshkumar Ge, Zhongming Potter, Amanda Mobley, Melissa W. Boussahmain, Chakib Feng, Yan Wishnok, John S. Fox, James G. |
| author_sort | Garcia, Alexis |
| collection | MIT |
| description | Author Manuscript: 2012 April 1. |
| first_indexed | 2024-09-23T11:19:18Z |
| format | Article |
| id | mit-1721.1/75430 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:19:18Z |
| publishDate | 2012 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/754302022-09-27T18:41:37Z H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response Helicobacter hepaticus–Induced Liver Tumor Promotion Is Associated with Increased Serum Bile Acid and a Persistent Microbial-Induced Immune Response Garcia, Alexis Zeng, Yu Muthupalani, Sureshkumar Ge, Zhongming Potter, Amanda Mobley, Melissa W. Boussahmain, Chakib Feng, Yan Wishnok, John S. Fox, James G. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Garcia, Alexis Zeng, Yu Muthupalani, Sureshkumar Ge, Zhongming Potter, Amanda Mobley, Melissa W. Boussahmain, Chakib Feng, Yan Wishnok, John S. Fox, James G. Author Manuscript: 2012 April 1. Chronic microbial infection influences cancer progression, but the mechanisms that link them remain unclear. Constitutive androstane receptor (CAR) is a nuclear receptor that regulates enzymes involved in endobiotic and xenobiotic metabolism. CAR activation is a mechanism of xenobiotic tumor promotion; however, the effects of chronic microbial infection on tumor promotion have not been studied in the context of CAR function. Here, we report that CAR limits the effects of chronic infection–associated progression of liver cancer. CAR knockout (KO) and wild-type (WT) male mice were treated with or without the tumor initiator diethylnitrosamine (DEN) at 5 weeks of age and then orally inoculated with Helicobacter hepaticus (Hh) or sterile media at 8 weeks of age. At approximately 50 weeks postinoculation, mice were euthanized for histopathologic, microbiological, molecular, and metabolomic analyses. Hh infection induced comparable hepatitis in WT and KO mice with or without DEN that correlated with significant upregulation of Tnfα and toll receptor Tlr2. Notably, DEN-treated Hh-infected KO mice exhibited increased numbers of liver lobes with dysplasia and neoplasia and increased multiplicity of neoplasia, relative to similarly treated WT mice. Enhanced tumor promotion was associated with decreased hepatic expression of P450 enzymes Cyp2b10 and Cyp3a11, increased expression of Camp, and increased serum concentrations of chenodeoxycholic acid. Together, our findings suggest that liver tumor promotion is enhanced by an impaired metabolic detoxification of endobiotics and a persistent microbial-induced immune response. Cancer Res; 71(7); 2529–40 National Institutes of Health (U.S.) (Grant R01CA067529) National Institutes of Health (U.S.) (Grant R01DK052413) National Institutes of Health (U.S.) (Grant T32RR007036) National Institutes of Health (U.S.) (Grant P30ES002109) National Institutes of Health (U.S.) (Grant P01CA026731) 2012-12-12T19:04:16Z 2012-12-12T19:04:16Z 2011-02 2010-11 Article http://purl.org/eprint/type/JournalArticle 0008-5472 1538-7445 http://hdl.handle.net/1721.1/75430 Garcia, A. et al. “Helicobacter hepaticus-Induced Liver Tumor Promotion Is Associated with Increased Serum Bile Acid and a Persistent Microbial-Induced Immune Response.” Cancer Research 71.7 (2011): 2529–2540. https://orcid.org/0000-0001-9307-6116 https://orcid.org/0000-0002-2325-552X en_US http://dx.doi.org/10.1158/0008-5472.CAN-10-1975 Cancer Research Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Garcia, Alexis Zeng, Yu Muthupalani, Sureshkumar Ge, Zhongming Potter, Amanda Mobley, Melissa W. Boussahmain, Chakib Feng, Yan Wishnok, John S. Fox, James G. H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title | H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title_full | H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title_fullStr | H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title_full_unstemmed | H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title_short | H. hepaticus-induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial-induced immune response |
| title_sort | h hepaticus induced liver tumor promotion is associated with increased serum bile acid and a persistent microbial induced immune response |
| url | http://hdl.handle.net/1721.1/75430 https://orcid.org/0000-0001-9307-6116 https://orcid.org/0000-0002-2325-552X |
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