Molecular Basis of Disordered Differentiation of Cancer Cells

• Project/Area Number: 19790265
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Yokohama City University
• Principal Investigator: OKUDELA Koji Yokohama City University, 医学部, 助教 (10326027)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: がん細胞 / 分化異状 / KRAS / 網羅的発現解析 / がん

Research Abstract

本研究の目的は、がん細胞に共通にみいだされる特徴である分化異状の誘導機構を明確にすることであった。申請者は、がん遺伝KRASが、上皮細胞に造血系・神経系の分化形質を誘導することをみいだし、その下流に位置する転写制御因子群に着目し、これらの分化異状への関与について検討した。候補とした分子のうちEGR1は細胞の扁平化、突起物の伸長を誘導した。HDAC9は核内封入体の形成を誘導した。ARID3Bはアポトーシスを誘導した。何れの分子も細胞増殖に抑制的に作用した。しかしながら、これらの単独ではKRASが引き起こしたような造血系・神経系細胞の分化形質を誘導に至らなかった。これらの結果から、特にEGR1はがん細胞の部分的に、特に形態学的な分化形質異状に関わる一分子基盤である可能性が考えられた。

Research Products

• [Journal Article] A case of epithelial-myoepithelial carcinoma of the bronchus-A review of reported cases and a comparison with other salivary gland-type carcinomas of the bronchus. (2009)
  • Author(s): Okudela K, Yazawa T, Tajiri M, Omori T, Takahashi K, Woo T, Shimoyamada H, Ogawa N, Kitamura H.
  • Journal Title: Pathol Res Pract. (in press)
• [Journal Article] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma: Its implication in carcinogenesis. (2009)
  • Author(s): Okudela K, Woo T, Yazawa T, Ogawa N, Tajiri M, Masuda M, Kitamura H.
  • Journal Title: Lung Cancer (in press)
• [Journal Article] Role of 3'-phosphoinositides in oncogenic KRAS-induced modulation of shape and motility of airway epithelial cells. (2009)
  • Author(s): Okudela K, Yazawa T, Suzuki T, Sugimura H, Kitamura H.
  • Journal Title: Pathol Int. 59(1) Pages: 28-37
• [Journal Article] Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas. (2009)
  • Author(s): Woo T, Okudela K, Yazawa T, Wada N, Ogawa N, Ishiwa N, Tajiri M, Rino Y, Kitamura H, Masuda M.
  • Journal Title: Lung Cancer (in press)
• [Journal Article] Small Cell Lung Cancer: Significance of RB Alterations and TTF-1 Expression in its Carcinogenesis, Phenotype, and Biology. (2009)
  • Author(s): Kitamura H, Yazawa T, Sato H, Okudela K, Shimoyamada H.
  • Journal Title: Endocr Pathol. 20(2) Pages: 101-107
• [Journal Article] Small Cell Lung Cancer : New Insights into its Carcinogenesis Mechanism and Aggressive Behavior. (2009)
  • Author(s): Kitamura H, Yazawa T, Okudela K, Sato H, Shimoyamada H.
  • Journal Title: Open Pathology Journal (in press)
• [Journal Article] Regulation of IGFBP4 in neuroendocrine carcinoma. (2009)
  • Author(s): Yazawa T, Sato H, Shimoyamada H, Okudela K, Kitamura H et al.
  • Journal Title: Am J Pathol (in press)
• [Journal Article] Significant association between EGFR-mutated lung adenocarc inoma and past illness from gastric cancer or uterine myoma : Its implication in carcinogenesis. (2009)
  • Author(s): OKUDELA-K, et.al.
  • Journal Title: Lung cancer (In press)
  • Peer Reviewed
• [Journal Article] Role of 3' -phosphoinositides in oncogenic KRAS-induced modu : ation of shape and motility of airway epithelial cells (2009)
  • Author(s): OKUDELA-K, et.al.
  • Journal Title: Pathology International 59 Pages: 28-37
  • Peer Reviewed
• [Journal Article] Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinomas (2009)
  • Author(s): WOO-T, OKUDELA-K, et.al.
  • Journal Title: Lung cancer (In press)
  • Peer Reviewed
• [Journal Article] Down-regulation of DUSP6 expression in lung cancers-its mechanism and potential role in carcinogenesis (2009)
  • Author(s): OKUDELA-K, et.al.
  • Journal Title: American Journal of Pathology (In press)
  • Peer Reviewed
• [Journal Article] Inverse relationship between the length of the EGFR CA repeat polymorphism in lung carcinoma and protein expression of EGFR in the carcinoma. (2008)
  • Author(s): Suzuki M, Kageyama S, Shinmura K, Okudela K, Bunai T, Nagura K, Igarashi H, Kiyose S, Mori H, Tao H, Goto M, Takamochi K, Mochizuki T, Suzuki K, Ohashi R, Ogawa H, Yamada T, Niwa H, Tsuneyoshi T, Sugimura H.
  • Journal Title: J Surg Oncol. 98(6) Pages: 457-461
• [Journal Article] PI3CA mutations and amplifications in human lung cancers (2007)
  • Author(s): OKUDELA-K, et. al.
  • Journal Title: Pathology International 57 Pages: 664-671
  • Peer Reviewed
• [Journal Article] Down-regulation of DUSP6 expression in lung cancers-its mechanism and potential role in carcinogenesis-.
  • Author(s): Okudela K, Yazawa T, Woo T, Kitamura H et al.
  • Journal Title: Am J Pathol (In press)
• [Presentation] 異型性の分子基盤(イオンチャンネル制御因子FXYD3の関与 (2009)
  • Author(s): 寺康司、矢澤卓也、下山田博明、禹哲漢、佐藤華子、武内智康、石井順、栄田昌史、後藤和也、宮田千恵、柏木維人、椙村春彦、北村均
  • Organizer: 日本病理学会総会
  • Place of Presentation: 京都
• [Presentation] A CA dinucleotide repeat length polymorphism of the first intron of epidermal growth factor receptor (EGFR) and EGFR alterations in Japanese lung cancers (2008)
  • Author(s): OKUDELA-K, et. al.
  • Organizer: 第12回世界肺癌学会(IASLC)
  • Place of Presentation: 韓国ソウル
  • Year and Date: 2008-09-06
• [Presentation] EGFR遺伝子変異を高感度かつ簡易に検出するオリゴヌクレオチドアレイの開発 (2008)
  • Author(s): 寺康司、五所尾康博、矢澤卓也、下山田博明、禹哲漢、北村均
  • Organizer: 日本病理学会総会
  • Place of Presentation: 石川