A Integrated Study of Pathological Significance of Cytosine Methylation of Non-CpG Island

• Project/Area Number: 19390100
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kobe University
• Principal Investigator: KITAZAWA Sohei Kobe University, 大学院・医学研究科, 客員教授 (90186239)
• Co-Investigator(Kenkyū-buntansha): TAKENAKA Atsuhi 鳥取大, 医, 教授 (50368669) ; KAJI Hiroshi 神戸大, 医, 特命准教授 (90346255) ; KITAZAWA Riko 神戸大, 医, 特命准教授 (00273780)
• Project Period (FY): 2007 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
• Keywords: 非CpCアイランド / メチル化 / 遺伝子プロモータ / 非CpGアイランド / 遺伝プロモータ / 膀胱癌 / 造血細胞 / 転写因子 / エピジェネティクス / CpG-island / DNAメチル化 / BANBI / 転写制御 / 副甲状腺過形成 / P16 / BAMBI

Research Abstract

Cytosine methylation in CpG-island, located usually regulatory region of many genes, is well recognized as an inhibitory epigenetic regulator. On the other hand, biological significance of the cytosine methylation other than CpG-island is unclear. By focusing morphology-oriented microscopic dissection methods, we analyzed cytosine methylation status of the BAMBI gene promoter in bladder cancer and of the P16 in renal tumor of diabetic rats, and found that some of the cytosine methylation outside of the CpG-island contributes to the tumor development and progression.

Research Products

• [Journal Article] Identification and analysis of function of a novel splicing variant of mouse receptor activator of NF-kappaB (2011)
  • Author(s): S.Mukai, et al.
  • Journal Title: Molecular and Cellular Biochemistry Volume: (in press)
  • Peer Reviewed
• [Journal Article] Epigenetic alteration by DNA promoter hypermethylation of genes related to transforming growth factor-β (TGF-β) signaling. (2011)
  • Author(s): Sann Sanda Khin, et al.
  • Journal Title: Cancers Volume: 3 Pages: 982-993
  • Peer Reviewed
• [Journal Article] Depressed expression of Klotho and FGFR1 in hyperplastic parathyroid glands from uremic patients. (2010)
  • Author(s): Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K, Tominaga Y, Otsuki N, Nibu K, Kitazawa R, Fukagawa M.
  • Journal Title: Kidney Int 77 Pages: 232-238
  • Peer Reviewed
• [Journal Article] Oxidative and nitrosative stress and progression of diabetic nephropathy in type 2 diabetes. (2010)
  • Author(s): Fujii H, Kono K, Nakai K, Goto S, Komaba H, Hamada Y, Shinohara M, Kitazawa R, Kitazawa S, Fukagawa M.
  • Journal Title: Am J Nephrol 31 Pages: 342-352
  • Peer Reviewed
• [Journal Article] Enhancement of ultraviolet B-induced skin tumor development in phospholipase C knockout mice is associated with decreased apoptosis. (2010)
  • Author(s): Oka M, Edamatsu H, Kunisada M, Dien S, Kitazawa R, Kataoka T, Nishigori C.
  • Journal Title: Carcinogeneis 31 Pages: 1897-1902
  • Peer Reviewed
• [Journal Article] Crucial role of the small GTPase Rac1 in insulin-stimulated translocation of glucose transporter 4 to the mouse skeletal muscle sarcolemma. (2010)
  • Author(s): S Ueda, et al.
  • Journal Title: FASEB J Volume: 24 Pages: 2254-2261
  • Peer Reviewed
• [Journal Article] BAMBI gene is epigenetically silenced in a subset of high-grade bladder cancer (2009)
  • Author(s): Sann Sanda Khin, Kitazawa R, Win N, Than TA, Mori K, Kondo T, Kitazawa S
  • Journal Title: Int J Cancer 125 Pages: 328-338
  • Peer Reviewed
• [Journal Article] BAMBI gene is epigenetically silenced in a subset of high-grade bladder cancer. (2009)
  • Author(s): Sann Sanda Khin, et al.
  • Journal Title: Int J Cancer 125 Pages: 328-338
  • Peer Reviewed
• [Journal Article] Ce promotes intestinal tumorigenesis of ApcMin/+ mice through augmentation of inflammation and angiogenesis. (2009)
  • Author(s): Li M., et al.
  • Journal Title: Carcinogenesis 30 Pages: 1424-1432
  • Peer Reviewed
• [Journal Article] Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia. (2009)
  • Author(s): Hamada Y., et al.
  • Journal Title: Bone 44 Pages: 936-941
  • Peer Reviewed
• [Journal Article] Dexamethasone Promotes Osteoclastogenesis by Inhibiting Osteoprotegerin through Multiple Levels (2008)
  • Author(s): Kondo T, Kitazawa R, Yamaguchi A, Kitazawa S
  • Journal Title: J Cell Biochem 103 Pages: 335-345
  • Peer Reviewed
• [Journal Article] Hypermethylation of Epithelial-cadherin Gene Promoter is Associated with Epstein-Barr Virus in Nasopharyngeal, Carcinoma (2008)
  • Author(s): Niemhom S, Kitazawa S, Kitazawa R, Maeda S, Leopairat J
  • Journal Title: Cancer Detect Prev 32 Pages: 127-134
  • Peer Reviewed
• [Journal Article] FSP27 Contributes to Efficient Energy Storage in Murine White Adipocytes by Promoting the Formation of Unilocular Lipid Droplets (2008)
  • Author(s): Nishino N, Tamori Y, Tateya S, Kawaguchi T, Shibakusa T, Mizunoya W, Inoue K, Kitazawa R, Kitazawa S, Matsuki Y, Hiramatsu R, Masubuchi S, Omachi A, Kimura K, Saito M, Amo T, Ohta S, Yamaguchi T, Osumi T, Cheng J, Fujimoto T, Nakao H, Nakao K, Aiba A, Okamura H, Fushiki T, Kasuga M
  • Journal Title: J Clin Invest 118 Pages: 2808-2821
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide Suppresses RANK Gene Expression in Macrophages by Down-Regulating PU.1 and MITF (2008)
  • Author(s): Ishii J, Kitazawa R, Mori K, McHugh K. P., Morii E, Kondo T, Kitazawa S
  • Journal Title: J Cellular Biochem 105 Pages: 896-904
  • Peer Reviewed
• [Journal Article] MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene Are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct (2008)
  • Author(s): Darwanto A, Kitazawa R, Kondo T, Kitazawa S
  • Journal Title: Acta Histochem Cytochem 41 Pages: 135-142
  • NAID: 130000070760
  • Peer Reviewed
• [Journal Article] Modulation of Mouse RANKL Gene Expression by Runx2 and Vitamin D3 (2008)
  • Author(s): Kitazawa R, Mori K, Yamaguchi A, Kondo T, Kitazawa S
  • Journal Title: J Cellular Biochem 105 Pages: 1289-1297
  • Peer Reviewed
• [Journal Article] Hepatic failure and enhanced oxidative stress in mitochondrial diabetes (2008)
  • Author(s): Takahashi Y, Iida K, Takeno R, Kitazawa R, Kitazawa S, Kitamura H, Fujioka Y, Yamada H, Kanda F, Ohta S, Nishimaki K, Fujimoto M, Kondo T, Iguchi G, Takahashi K, Kaji H, Okimura Y, Chihara K
  • Journal Title: Endocr J 55 Pages: 509-514
  • NAID: 10021266426
  • Peer Reviewed
• [Journal Article] MeCP2 Expression and Promoter Methylation of Cyclin D1 Gene are Associated with Cyclin D1 Expression in Developing Rat Epididymal Duct (2008)
  • Author(s): Darwanto A, Kitazawa R, Kondo T, Kitazawa S
  • Journal Title: Acta Histochem Cytochem 41 Pages: 135-142
  • NAID: 130000070760
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide Suppresses RANK Gene Expression in Macrophages by Down-Regulating PU. 1 and MITF (2008)
  • Author(s): Ishii J, Kitazawa R, Mori K, McHugh K. P., Morii E, Kondo T, Kitazawa S
  • Journal Title: J Cellular Biochem 105 Pages: 896-904
  • Peer Reviewed
• [Journal Article] Hypermethylation of Epithelial-cadherin Gene Promoter is Associated with Epstein-Barr Virus in Nasopharyngeal Carcinoma (2008)
  • Author(s): Niemhom S, Kitazawa S, Kitazawa R, Maeda S, Leopairat J
  • Journal Title: Cancer Detect Prev 32 Pages: 127-134
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide suppresses RANK gene expression by macrophage through the down-regulation of PU. 1 and MITF. (2008)
  • Author(s): Ishii J., et al.
  • Journal Title: J Cell Biochem 105 Pages: 896-904
  • Peer Reviewed
• [Journal Article] Modulation of mouse RANKL gene expression by Runx2 and vitamin D3 pathway. (2008)
  • Author(s): Kitazawa R., et al.
  • Journal Title: J Cell Biochem 105 Pages: 1289-1297
  • Peer Reviewed
• [Journal Article] MeCP2 expression and promoter methylation of cyclin D1 gene are associated with cyclin D1 expression in developing rat epididymalduct. (2008)
  • Author(s): Darwanto A., et al.
  • Journal Title: Acta Histochem Cytochem 41 Pages: 135-142
  • Peer Reviewed
• [Journal Article] Methylation Status of a Single CpG Locus 3 Bases Upstream of TATA-box of RANKL Gene Promoter Modulates Cell- and Tissue-specific RANKL Expression and Osteoclastogenesis (2007)
  • Author(s): Kitazawa R, Kitazawa S
  • Journal Title: Mol Endocrinology 21 Pages: 148-158
  • Peer Reviewed
• [Journal Article] Dexamethasone Promotes Osteoclastogenesis by Inhibiting Osteoprotegerin through Multiple Levels. (2007)
  • Author(s): Kondo T., et. al.
  • Journal Title: J Cell Biochem 103 Pages: 335-345
  • Peer Reviewed
• [Journal Article] Histomorphometric Analysis of Diabetic Osteopenia in Streptozotocin-induced Diabetic Mice: a Possible Role of Oxidative Stress. (2007)
  • Author(s): Hamada Y., et. al.
  • Journal Title: Bone 40 Pages: 938-943
  • Peer Reviewed
• [Journal Article] Unsuspected Uterine Leiomyosarcoma: MR Imaging Findings before and after Focused Ultrasound Surgery(FUS) (2007)
  • Author(s): Fukunishi H., et. al.
  • Journal Title: Int J Gynecolog Cancer 17 Pages: 724-728
  • Peer Reviewed
• [Journal Article] Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer (review)
  • Author(s): Sann Sanda Khin, Kitazawa R, Kondo T, Idei Y, Fujimoto M, Haraguchi R, Mori K, Kitazawa S
  • Journal Title: Cancers in press
  • Peer Reviewed
• [Journal Article] Identification and analysis of function of a novel splicing variant of mouse receptor activator of NF-kappaB.
  • Author(s): Mukai S, Kitazawa R, Ishii J, Kondo T, Hakozaki A, Hosiuchi K, Kiyoshi M, Kitazawa S.
  • Journal Title: Mol Cell Biochem in press
  • Peer Reviewed
• [Journal Article] Parathyroid hormone-responsive Smad3-related factor, Tmem119, promotes osteoblast differentiation and interacts with the bone morphogenetic protein-Runx2 pathway.
  • Author(s): Hisa I, Inoue Y, Hendy GN, Canaff L, Kitazawa R, Kitazawa S, Komori T, Sugimoto T, Seino S, Kaji H
  • Journal Title: J Biol Chem in press
  • Peer Reviewed
• [Presentation] ラット酸化的ストレスモデルにおける腎腫瘍発生初期に生じるエピジェネティクス変化の解析 (2010)
  • Author(s): 北澤荘平, 他
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2010-04-27
• [Presentation] RANKL upregulates mouse RANK gene transcriptionthrough the NFAT binding site of RANK gene promoter. (2010)
  • Author(s): Riko Kitazawa, Junko Ishii, Satomi Mukai, Takeshi Kondo, Michiko Mori, Kiyoshi Mori, Sohei Kitazawa
  • Organizer: 第10回世界骨粗鬆症学会
  • Place of Presentation: フィレンツェ、イタリア
• [Presentation] Derepression of mouse SFRP-4 gene expression by oxidative stress : A plausible mechanism leading to low-turnover osteoporosis in diabetes and senscence. (2010)
  • Author(s): Kiyoshi Mori, Riko Kitazawa, Takeshi Kondo, Satomi Mukai, Michiko Mori, Sohei Kitazawa
  • Organizer: 第10回世界骨粗鬆症学会
  • Place of Presentation: フィレンツェ、イタリア
• [Presentation] Identification and functional analysis of a novel splicing variant of mouse RANK. (2010)
  • Author(s): Satomi Mukai, Riko Kitazawa, Junko Ishii, Takeshi Kondo, Akihiro Hakozaki, Keisuke Horiuchi, Kiyoshi Mori, Sohei Kitazawa
  • Organizer: 第14回国際内分泌学会
  • Place of Presentation: 京都
• [Presentation] マウスRANK遺伝子転写におけるNFATの機能解析 (2009)
  • Author(s): 北澤理子, 他
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館(京都府)
  • Year and Date: 2009-05-03
• [Presentation] 転写早期の新生mRNAの電子顕微鏡による動態解析 (2008)
  • Author(s): 北洋荘平, 他
  • Organizer: 第49回日本組織細胞化学会総会シンポジウム
  • Place of Presentation: 長崎
  • Year and Date: 2008-10-05
• [Presentation] BAMBI gene is epigenetically silenced in a subset of high-grade bladder cancer. (2008)
  • Author(s): Sohei Kitazawa, Sann Sanda Khin, Kiyoshi Mori, Takeshi Kondo, Riko Kitazawa
  • Organizer: 第30回米国骨代謝学会議
  • Place of Presentation: デンバー, USA
• [Presentation] 日本、ミャンマー両国の膀胱腫瘍発生に関するエピジェネティクス解析 (2007)
  • Author(s): Sann Sanda Khin
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [Presentation] STZ誘発糖尿病モデルラットにおける腎腫瘍発生初期におけるエピジェネティクス変化の解析 (2007)
  • Author(s): 北澤荘平, 森清, 近藤武史, 北澤理子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Modulation of mouse RANKL gene expression by Runx2 and vitamin D3 . (2007)
  • Author(s): Riko Kitazawa, Kiyoshi Mori, Takeshi Kondo, Sohei Kitazawa
  • Organizer: 第29回米国骨代謝学会議
  • Place of Presentation: ハワイ, USA
• [Presentation] Molecular cloning and characterization of mouse RANK gene promoter region (2007)
  • Author(s): Junko Ishii, Riko Kitazawa, Takeshi Kondo, Mori K, Kevin P McHugh, Sohei Kitazawa
  • Organizer: 第29回米国骨代謝学会議
  • Place of Presentation: ハワイ, USA
• [Presentation] 日本とミャンマーにおける膀胱腫瘍進展過程におけるBAMBI遺伝子のエピジェネティクス制御の変化 (2007)
  • Author(s): サンサンダキン, 北澤理子, 近藤武史, 森清, タイタンエイ, ネウイン, 北澤荘平
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] In situ detection of specific gene expression during and immediately after transcription at electron microscopic level. In Microscopy : Science, Technology, Applications and Education (2011)
  • Author(s): S.Kitazawa, et al
  • Total Pages: 200
  • Publisher: Formatex Research Center, Spain
• [Book] 組織細胞化学2010-組織細胞化学イメージングの基礎と最前線:生体内分子局在と機能を探る-日本組織細胞化学会編集 エピジェネティクスと病理組織学的変 (2010)
  • Author(s): 北澤荘平, 森清, 近藤武史, 北澤理子
• [Book] DNA Methylation Research Trends(Editor ; Kobayashi TB, Epigenetic roles of CpG methylation at non-CpG-islands revealed by morphology-oriented epigenetic research) (2007)
  • Author(s): Kitazawa S, Mori K, kondo T, Fujimoto M, Kitazawa R
  • Publisher: Nova Science Publishers
• [Book] DNA Methylation Research Trends (2007)
  • Author(s): T. B. Kobayashi
  • Total Pages: 200
  • Publisher: Nova Science Publishers Inc
• [Book] DNA Methylation Research Trends, Epigenetic roles of CpG methylation at non-CpG-islands revealed by morphology-oriented epigenetic research(Editor; Kobayashi TB)
  • Author(s): Kitazawa S, Mori K, Kondo T, Fujimoto M, Kitazawa R
• [Remarks] ホームページ等
  • URL: http://www.med.kobe-u.ac.jp/patho2/index.html