title: Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
abstract: We report that HMGN1, a nucleosome-binding protein that affects chromatin structure and function, affects the growth of N-nitrosodiethylamine (DEN)-induced liver tumors. Following a single DEN injection at 2 weeks of age, Hmgn1(tm1/tm1) mice, lacking the nucleosome-binding domain of HMGN1, had earlier signs of liver tumorigenesis than their Hmgn1(+/+) littermates. Detailed gene expression profiling revealed significant differences between DEN-injected and control saline-injected mice, but only minor differences between the injected Hmgn1(tm1/tm1) mice and their Hmgn1(+/+) littermates. Pathway analysis revealed that the most significant process affected by loss of HMGN1 involves the lipid/sterol metabolic pathway. Our study indicates that in mice, loss of HMGN1 leads to transcription changes that accelerate the progression of DEN-induced hepatocarcinogenesis, without affecting the type of tumors or the final total tumor burden of these mice.
  
  
  CONCLUSIONS
  Loss of HMGN1 leads to accelerated progression of DEN-induced hepatocarcinogenesis in mice.
authors.affiliation: NIH, 37 Convent Dr #3122, Bethesda, MD 20892-4255. postniky@mail.nih.gov.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Postnikov
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Factor
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002843:Chromatin / Q000235:genetics; D004052:Diethylnitrosamine / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D024241:HMGN1 Protein / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D047368:Tumor Burden
chemical_list: D002843:Chromatin; D024241:HMGN1 Protein; D004052:Diethylnitrosamine