机构：[a]Department of Surgical Oncology, Cancer Treatment Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China[b]Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ, USA[c]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China普通外科首都医科大学宣武医院[d]Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA[e]Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA[f]Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA[g]Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA
Farnesoid X receptor (FXR, Nr1h4) and small heterodimer partner (SHP, Nr0b2) are nuclear receptors that are critical to liver homeostasis. Induction of SHP serves as a major mechanism of FXR in suppressing gene expression. Both FXR-/- and SHP-/- mice develop spontaneous hepatocellular carcinoma (HCC). SHP is one of the most strongly induced genes by FXR in the liver and is a tumor suppressor, therefore, we hypothesized that deficiency of SHP contributes to HCC development in the livers of FXR-/- mice and therefore, increased SHP expression in FXR-/- mice reduces liver tumorigenesis. To test this hypothesis, we generated FXR-/- mice with overexpression of SHP in hepatocytes (FXR-/-/-SHPTg) and determined the contribution of SHP in HCC development in FXR-/- mice. Hepatocyte-specific SHP overexpression did not affect liver tumor incidence or size in FXR-/- mice. However, SHP overexpression led to a lower grade of dysplasia, reduced indicator cell proliferation and increased apoptosis. All tumor-bearing mice had increased serum bile acid levels and IL-6 levels, which was associated with activation of hepatic STAT3. In conclusion, SHP partially protects FXR-/- mice from HCC formation by reducing tumor malignancy. However, disrupted bile acid homeostasis by FXR deficiency leads to inflammation and injury, which ultimately results in uncontrolled cell proliferation and tumorigenesis in the liver. (C) 2013 Elsevier Inc. All rights reserved.
第一作者机构：[a]Department of Surgical Oncology, Cancer Treatment Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
推荐引用方式(GB/T 7714)：
Guodong Li,Bo Kong,Yan Zhu,et al.Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice[J].TOXICOLOGY AND APPLIED PHARMACOLOGY.2013,272(2):299-305.doi:10.1016/j.taap.2013.06.016.
APA：
Guodong Li,Bo Kong,Yan Zhu,Le Zhan,Jessica A. Williams...&Grace L. Guo.(2013).Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice.TOXICOLOGY AND APPLIED PHARMACOLOGY,272,(2)
MLA：
Guodong Li,et al."Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice".TOXICOLOGY AND APPLIED PHARMACOLOGY 272..2(2013):299-305
