Epigenomic analysis for Barrette's esophagus and carcinomas

• Project/Area Number: 24790729
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: 独立行政法人国立国際医療研究センター
• Principal Investigator: OTSUBO Takeshi 独立行政法人国立国際医療研究センター, 消化器疾患研究部, 特任研究員 (00623034)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 上部消化管学（食道、胃、 十二指腸） / エピゲノム / 上部消化管学（食道、胃、十二指腸）

Research Abstract

In this study, we aim to identify the epigenetic alterations underlying Barrett's esophagus (BE) and esophageal squamous cell carcinomas (ESCCs). First, we assessed the abnormal glycosylation in human esophageal specimens, and found that cell surface expression of Sd(a) were ectopically induced in BE, whereas down-regulated in BE adenocarcinomas (BEAs) with promoter DNA hypermethylation. Second, we performed methylome and transcriptome analyses with ESCC tissues, and found that some promoter DNA hypermethylated genes were functionally related to cell proliferation and adhesion of ESCC cell lines. Thus, we demonstrated that the aberrant epigenetic alterations positively contribute to BEAs and ESCCs.

Research Products

• [Journal Article] The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells. (2014)
  • Author(s): Obata, Y., Furusawa, Y., Endo, T. A., Sharif, J., Takahashi, D., Atarasho, K., Nakayama, M., Onawa, S., Fujimura, Y., Takahashi, M., Ikawa, T., Otsubo, T., Kawamura, Y. I., Dohi, T., Tajima, S., Masumoto, H., Ohara, O., Honda, K., Hori, S., Ohno, H., Koseki, H., Hase, K
  • Journal Title: Nat Immunol Volume: 15(6) Pages: 571-579
• [Journal Article] A. Enhancement of leptin receptor signaling by SOCS3 deficiency induces development of gastric tumors in mice (2014)
  • Author(s): Inagaki-Ohara, K., Mayuzumi, H., Kato, S., Minokoshi, Y., Otsubo, T., Kawamura, Y. I., Dohi, T., Matsuzaki, G., Yoshimura
  • Journal Title: Oncogene Volume: 33(1) Pages: 74-84
• [Presentation] Cell type-specific, genome-wide epigenetic analysis for lamina propria cells isolated from the colon with ulcerative colitis (2013)
  • Author(s): 大坪武史
  • Organizer: 第42回日本免疫学会学術総会
  • Place of Presentation: 幕張,千葉,日本
  • Year and Date: 2013-12-11
• [Presentation] バレット食道および食道腺癌細胞における DNAメチル化異常 (2013)
  • Author(s): 萩原輝記
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜,日本
  • Year and Date: 2013-09-13
• [Presentation] DNA methylation in cell regeneration and cancer in ulcerativecolitis (2013)
  • Author(s): 土肥多惠子
  • Organizer: The 2nd JSGE International Topic Conference-Inflammation and Carcinogenesis of Digestive Organs
  • Place of Presentation: 鹿児島,日本
  • Year and Date: 2013-03-23
• [Presentation] 潰瘍性大腸炎粘膜固有層における少数のT細胞及びマクロファージ/樹状細胞を用いたエピゲノム解析 (2012)
  • Author(s): 大坪武史
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡,日本
  • Year and Date: 2012-12-16
• [Presentation] バレット食道および食道腺癌細胞におけるエピゲノム解析 (2012)
  • Author(s): 萩原輝記
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡,日本
  • Year and Date: 2012-12-16
• [Presentation] Genome-wide Epigenomic Analysis of Lamina Propria Mononuclear Cells Isolated from Patients with Inflammatory Bowel Disease (2012)
  • Author(s): 河村由紀
  • Organizer: The 6th Japan & US Collaboration Conference in Gastroenterology
  • Place of Presentation: 東京,日本
  • Year and Date: 2012-11-15
• [Presentation] Genome-Wide Epigenomic Analysis of Lamina Propria Mononuclear Cellsof Inflammatory Bowel Disease (2012)
  • Author(s): 大坪武史
  • Organizer: Digestive Disease Week
  • Place of Presentation: SanDiego, CA,USA
  • Year and Date: 2012-05-22
• [Presentation] Involvement of L1 retrotransposition in murine experimental colitis-cancer model.
  • Author(s): 大坪武史
  • Organizer: 2013 Digestive Disease Week
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Cell type-specific, genome-wide epigenetic analysis for lamina propria cells isolated from the colon with ulcerative colitis
  • Author(s): 大坪武史
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張、千葉、日本
• [Presentation] Genome-Wide Epigenomic Analysis of Lamina Propria Mononuclear Cells of Inflammatory Bowel Disease.
  • Author(s): 大坪武史
  • Organizer: 2012 Digestive Disease Week
  • Place of Presentation: San Diego, CA, USA
• [Presentation] 潰瘍性大腸炎粘膜固有層における少数のT細胞及びマクロファージ/樹状細胞を用いたエピゲノム解析
  • Author(s): 大坪武史
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡、日本
• [Presentation] バレット食道および食道腺癌細胞におけるエピゲノム解析
  • Author(s): 萩原輝記
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡、日本