title: Elevated HMGN4 expression potentiates thyroid tumorigenesis.
abstract: Thyroid cancer originates from genetic and epigenetic changes that alter gene expression and cellular signaling pathways. Here, we report that altered expression of the nucleosome-binding protein HMGN4 potentiates thyroid tumorigenesis. Bioinformatics analyses reveal increased HMGN4 expression in thyroid cancer. We find that upregulation of HMGN4 expression in mouse and human cells, and in the thyroid of transgenic mice, alters the cellular transcription profile, downregulates the expression of the tumor suppressors Atm, Atrx and Brca2, and elevates the levels of the DNA damage marker γH2AX. Mouse and human cells overexpressing HMGN4 show increased tumorigenicity as measured by colony formation, by tumor generation in nude mice, and by the formation of preneoplastic lesions in the thyroid of transgenic mice. Our study identifies a novel epigenetic factor that potentiates thyroid oncogenesis and raises the possibility that HMGN4 may serve as an additional diagnostic marker, or therapeutic target in certain thyroid cancers.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Kugler
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Postnikov
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Furusawa
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: Shioko
authors.initials: S
authors.lastname: Kimura
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D024001:HMGN Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000235:genetics; D013961:Thyroid Gland / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D024001:HMGN Proteins; C028567:HMGN4 protein, human