Genetic Predisposition to Hepatocarcinogenesis in Inbred and Outbred Mouse Lines Selected for High or Low Inflammatory Response

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-α, IL-1β, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

[1]  Pingyi Liu,et al.  Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy , 2018, Journal of immunology research.

[2]  A. Walker,et al.  Host genetic factors associated with hepatocellular carcinoma in patients with hepatitis C virus infection: A systematic review , 2018, Journal of viral hepatitis.

[3]  G. FitzGerald,et al.  Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury , 2017, Molecular metabolism.

[4]  J. Andersen,et al.  Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury , 2017, Proceedings of the National Academy of Sciences.

[5]  Dong Dong,et al.  Systematic analyses and comprehensive field synopsis of genetic association studies in hepatocellular carcinoma , 2016, Oncotarget.

[6]  R. Schwabe,et al.  Serum Amyloid A Induces Inflammation, Proliferation and Cell Death in Activated Hepatic Stellate Cells , 2016, PloS one.

[7]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[8]  T. Dragani,et al.  Mouse Pulmonary Adenoma Susceptibility 1 Locus Is an Expression QTL Modulating Kras-4A , 2014, PLoS genetics.

[9]  Klaus Schughart,et al.  Systems Genetics of Liver Fibrosis: Identification of Fibrogenic and Expression Quantitative Trait Loci in the BXD Murine Reference Population , 2014, PloS one.

[10]  T. Dragani,et al.  Genetic control of renal tumorigenesis by the mouse Rtm1 locus , 2013, BMC Genomics.

[11]  T. Dragani,et al.  Genetic linkage analysis identifies Pas1 as the common locus modulating lung tumorigenesis and acute inflammatory response in mice , 2013, Genes and Immunity.

[12]  S. Milstien,et al.  Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond , 2013, Nature Reviews Drug Discovery.

[13]  Masahira Hattori,et al.  Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome , 2013, Nature.

[14]  H. Göring,et al.  Tissue specificity of genetic regulation of gene expression , 2012, Nature Genetics.

[15]  Zhaoyu Li,et al.  Foxa1 and Foxa2 Are Essential for Sexual Dimorphism in Liver Cancer , 2012, Cell.

[16]  J. Blangero,et al.  Diverse biological activities of the vascular non-inflammatory molecules - the Vanin pantetheinases. , 2012, Biochemical and biophysical research communications.

[17]  J. Marvel,et al.  Sequential desensitization of CXCR4 and S1P5 controls natural killer cell trafficking. , 2011, Blood.

[18]  T. Dragani,et al.  Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice , 2011, Genes and Immunity.

[19]  Junji Furuse,et al.  The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. , 2010, The oncologist.

[20]  T. Dragani,et al.  Genetic heterogeneity of inflammatory response and skin tumorigenesis in phenotypically selected mouse lines. , 2010, Cancer letters.

[21]  T. Dragani,et al.  Transcriptome of normal lung distinguishes mouse lines with different susceptibility to inflammation and to lung tumorigenesis. , 2010, Cancer letters.

[22]  T. Dragani,et al.  Genetic Control of IL-1β Production and Inflammatory Response by the Mouse Irm1 Locus , 2010, The Journal of Immunology.

[23]  Pei-Jer Chen,et al.  Gender Disparity of Hepatocellular Carcinoma: The Roles of Sex Hormones , 2010, Oncology.

[24]  T. Dragani,et al.  Risk of HCC: genetic heterogeneity and complex genetics. , 2010, Journal of hepatology.

[25]  Jun Hee Lee,et al.  Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression , 2010, Cell.

[26]  J. Chun,et al.  T-bet–dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow , 2009, The Journal of experimental medicine.

[27]  N. Starobinas,et al.  Gene expression profiles of bone marrow cells from mice phenotype‐selected for maximal or minimal acute inflammations: searching for genes in acute inflammation modifier loci , 2009, Immunology.

[28]  B. Gao,et al.  Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases , 2009, Journal of leukocyte biology.

[29]  E. Solary,et al.  Human defensins as cancer biomarkers and antitumour molecules. , 2009, Journal of proteomics.

[30]  C. Dinarello,et al.  Immunological and inflammatory functions of the interleukin-1 family. , 2009, Annual review of immunology.

[31]  S. Assefa,et al.  Role of sex steroid receptors in pathobiology of hepatocellular carcinoma. , 2008, World journal of gastroenterology.

[32]  T. Moll,et al.  Protection of Murine Systemic Lupus by the Ea Transgene without Expression of I-E Heterodimers1 , 2008, The Journal of Immunology.

[33]  T. Dragani,et al.  Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus , 2008, Hepatology.

[34]  S. Fukushima,et al.  Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo. , 2007, Cancer research.

[35]  Michael Karin,et al.  References and Notes Supporting Online Material Materials and Methods Som Text Figs. S1 to S6 Tables S1 to S4 Gender Disparity in Liver Cancer Due to Sex Differences in Myd88-dependent Il-6 Production , 2022 .

[36]  T. Lawrence,et al.  Sex, Cytokines, and Cancer , 2007, Science.

[37]  R. Kaneno,et al.  Enhanced natural killer activity and production of pro‐inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax) , 2007, Immunology.

[38]  H. Alexander,et al.  Journal of Translational Medicine Interleukin-1 and Cancer Progression: the Emerging Role of Interleukin-1 Receptor Antagonist as a Novel Therapeutic Agent in Cancer Treatment , 2022 .

[39]  A. Surprenant,et al.  Pannexin‐1 mediates large pore formation and interleukin‐1β release by the ATP‐gated P2X7 receptor , 2006, The EMBO journal.

[40]  M. Di Maio,et al.  Hormonal Treatment of Human Hepatocellular Carcinoma , 2006, Annals of the New York Academy of Sciences.

[41]  M. Seman,et al.  Inverse genetic predisposition to colon versus lung carcinogenesis in mouse lines selected based on acute inflammatory responsiveness. , 2005, Carcinogenesis.

[42]  J. Marrero,et al.  Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. , 2005, Journal of hepatology.

[43]  M. Seman,et al.  Convergent alteration of granulopoiesis, chemotactic activity, and neutrophil apoptosis during mouse selection for high acute inflammatory response , 2003, Journal of leukocyte biology.

[44]  P. Demant,et al.  Cancer susceptibility in the mouse: genetics, biology and implications for human cancer , 2003, Nature Reviews Genetics.

[45]  T. Dragani,et al.  Pulmonary adenoma susceptibility 1 (Pas1) locus affects inflammatory response , 2003, Oncogene.

[46]  B. Alter.  Cancer in Fanconi anemia, 1927–2001 , 2003, Cancer.

[47]  G. Beauchamp,et al.  Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ x 129P3/J F2 intercross. , 2002, Genome research.

[48]  L. Castagnetta,et al.  Epidemiology, Risk Factors, and Natural History of Hepatocellular Carcinoma , 2002, Annals of the New York Academy of Sciences.

[49]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[50]  A. Saran,et al.  Effect of genetic modification of acute inflammatory responsiveness on tumorigenesis in the mouse. , 1998, Carcinogenesis.

[51]  W. Cabrera,et al.  Genetics of nonspecific immunity: I. Bidirectional selective breeding of lines of mice endowed with maximal or minimal inflammatory responsiveness , 1992, European journal of immunology.

[52]  T. Lawrence,et al.  Cancer. Sex, cytokines, and cancer. , 2007, Science.

[53]  Chris Haley,et al.  GridQTL: A Grid Portal for QTL Mapping of Compute Intensive Datasets. , 2006 .

[54]  K. Rao,et al.  Carcinogenicity of diethylnitrosamine in newborn, infant, and adult mice , 2004, Journal of Cancer Research and Clinical Oncology.

[55]  G. Williams,et al.  N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. , 1996, Pharmacology & therapeutics.

[56]  Sb,et al.  Cancer in Fanconi Anemia , 2022 .