Analysis of expression mechanisms of neuroendocrine cancer cell-specific molecules via TTF-1

• Project/Area Number: 21590376
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kyorin University (2011); Yokohama City University (2009-2010)
• Principal Investigator: YAZAWA Takuya 杏林大学, 医学部, 准教授 (50251054)
• Co-Investigator(Kenkyū-buntansha): OKUDELA Koji 横浜市立大学, 医学部, 助教 (10326027) ; SHIMOYAMADA Hiroaki 杏林大学, 医学部, 助教 (60381472) ; SATO Hanako 聖マリアンナ医科大学, 医学部, 助教 (60438132) ; KITAMURA Hitoshi 横浜市立大学, 大学院・医学研究科, 教授 (20094302)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 肺がん / 悪性神経内分泌細胞 / TTF-1 / 肺癌 / 悪性神経内分泌腫瘍

Research Abstract

Thyroid transcription factor-1(TTF-1) is frequently expressed in lung adenocarcinomas with peripheral airway epithelium-like phenotype. However, frequent and abundant TTF-1 expression is also paradoxically found in small cell lung cancers, which commonly generate from central airway. The aim of this study was to investigate the expression mechanism of TTF-1 and search downstream molecules regulated by TTF-1.Through this study, it was suggested that TTF-1 expression was not epigenetically regulated and that TTF-1 complicatedly regulated gene expression with other homeobox transcription factors and neuroendocrine-specific basic helix-loop-helix transcription factors cooperatively.

Research Products

• [Journal Article] Differences of molecular expression mechanisms among neural cell adehesion molecule 1, synaptophysin, and chromogranin A in lung cancer cells (2012)
  • Author(s): Kashiwagi K, Ishii J, Sakaeda M, Arimasu Y, Shimoyamada H, Sato H, Miyata C, Kamma H, Aoki I, Yazawa T.
  • Journal Title: Pathol Int Volume: 62 Pages: 232-245
  • Peer Reviewed
• [Journal Article] CT analysis of the effect of piefenidone in patients with idiopathic pulmonary fibrosis (2012)
  • Author(s): Iwasawa T, Ogura T, Sakai F, Kanauchi T, Komagata T, Baba T, Gotoh T, Morita S, Yazawa T, Inoue T
  • Journal Title: Eur J Radiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Lung-term survivor with pulmonary veno-occlusive disease (2012)
  • Author(s): Matsushita K, Kanna M, Yazawa T, Shimizu S, Nitta M, Takamizawa T, Arakawa K, Yano H, Nishikawa M, Himeno H.
  • Journal Title: Circulation Volume: 125 Pages: 503-506
  • Peer Reviewed
• [Journal Article] Differences of molecular expression mechanisms among neural cell adhesion molecule 1, synaptophysin, and chrmogranin A in lung cancer cells (2012)
  • Author(s): Kashiwagi K, Ishii J, Sakaeda M, Arimasu Y, Shimoyamada H, Sato H, Miyata C, Kamma H, Aoki I, Yazawa T
  • Journal Title: Pathol Int Volume: VOL.62 Issue: 4 Pages: 232-245
  • DOI: 10.1111/j.1440-1827.2011.02781.x
  • Peer Reviewed
• [Journal Article] 内分泌腫瘍の病理 (2012)
  • Author(s): 菅間博, 矢澤卓也
  • Journal Title: 日本内分泌・甲状腺外科学会雑誌 Volume: 29巻 Pages: 57-61
  • NAID: 130004600528
  • Peer Reviewed
• [Journal Article] Insulin-like growth factor binding protein-4 gene silencing in lung adenocarcinomas (2011)
  • Author(s): Sato H, Sakaeda M, Ishii J, Kashiwagi K, Shimoyamada H, Okudela K, Tajiri M, Ohmori T, Ogura T, Woo T, Masuda M, Hirata K, Kitamura H, Yazawa T.
  • Journal Title: Pathol Int Volume: 61 Pages: 19-27
  • NAID: 10031185042
  • Peer Reviewed
• [Journal Article] Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin in mice (2011)
  • Author(s): Sakamoto S, Yazawa T, Baba Y, Sato H, Kanegae Y, Hirai T, Saito I, Goto T, Kurahashi K.
  • Journal Title: Am J Respir Cell Mol Biol Volume: 45 Pages: 489-497
  • Peer Reviewed
• [Journal Article] Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin in mice (2011)
  • Author(s): Sakamoto S, Yazawa T, Baba Y, Sato H, Kanegae Y, HiraiT, Saito I, Goto T, Kurahashi K
  • Journal Title: Am J Respir Cell Mol Biol Volume: VOL.45 Pages: 489-497
  • Peer Reviewed
• [Journal Article] Prognostic value of CD133 expression in stage I lung adenocarcinomas (2010)
  • Author(s): Woo T, Okudela K, Mitsui H, Yazawa T, Ogawa N, Tajiri M, Yamamoto T, Rino Y, Kitamura H, Masuda M.
  • Journal Title: Int J Clin Exp Pathol Volume: 4 Pages: 32-42
  • Peer Reviewed
• [Journal Article] Pneumothorax and idiopathic pulmonary fibrosis (2010)
  • Author(s): Iwasawa T, Ogura T, Takahashi H, Asakura A, Gotoh T, Yazawa T, Inoue T.
  • Journal Title: Jpn J Radiol Volume: 28 Pages: 672-679
  • NAID: 50007725087
  • Peer Reviewed
• [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 (2010)
  • 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 Volume: 206 Pages: 121-129
  • Peer Reviewed
• [Journal Article] Morphometric profiling of lung cancers. its association with clinicopathologic, biologic, and molecular genetic features (2010)
  • Author(s): Okudela K, Woo T, Mitsui H, Yazawa T, Shimoyamada H, Tajiri M, Ogawa N, Masuda M, Kitamura H.
  • Journal Title: Am J Surg Pathol Volume: 34 Pages: 243-255
  • Peer Reviewed
• [Journal Article] Proposal of an improved histological sub-typing system for lung adenocarcinoma. significant prognostic values for stage I disease (2010)
  • Author(s): Okudela K, Woo T, Mitsui H, Yazawa T, Shimoyamada H, Tajiri M, Ogawa N, Masuda M, Kitamura H.
  • Journal Title: Int J Clin Exp Pathol Volume: 25 Pages: 348-366
  • Peer Reviewed
• [Journal Article] Early growth response-1 induces and enhances vascular endothelial growth factor-A expression in lung cancer cells (2010)
  • Author(s): Shimoyamada H, Yazawa T, Sato H, Okudela K, Ishii J, Sakaeda M, Kashiwagi K, Suzuki T, Mitsui H, Woo T, Tajiri M, Ohmori T, Ogura T, Masuda M, Oshiro H, Kitamura H.
  • Journal Title: Am J Pathol Volume: 177 Pages: 70-83
  • Peer Reviewed
• [Journal Article] Proposal of an improved histological sub-typing system for lung adenoca rcinoma-significant prognostic values for stage I disease (2010)
  • Author(s): Yazawa T (Okudela K)
  • Journal Title: Int J Clin Exp Pathol Volume: 3 Pages: 348-366
  • Peer Reviewed
• [Journal Article] Morphometric profiling of lung cancers-Its association with clinicopathologic, biologic, and molecular genetic features (2010)
  • Author(s): Okudela K, Yazawa T, et al.
  • Journal Title: American Journal of Surgical Pathology 34 Pages: 243-255
  • Peer Reviewed
• [Journal Article] Caveolin gene transfer improves glucose metabolism in diabetic mice (2010)
  • Author(s): Otsu K, Yazawa T, et al.
  • Journal Title: American Journal of Physiology and Cell Physiology 298
  • Peer Reviewed
• [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 (2010)
  • Author(s): Okudela K, Yazawa T, et al.
  • Journal Title: Pathology Research and Practice 206 Pages: 121-129
  • Peer Reviewed
• [Journal Article] Prognostic value of KRAS mutations and Ki-67 expression in stage I lung adenocarcinoma (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 Volume: 65 Pages: 355-362
  • Peer Reviewed
• [Journal Article] Assessment of prognosis of patients with idiopathic pulmonary fibrosis by computer-aided analysis of CT images (2009)
  • Author(s): Iwasawa T, Asakura A, Sakai F, Kanauchi T, Gotoh T, Ogura T, Yazawa T, Nishimura J, Inoue T.
  • Journal Title: J Thorac Imaging Volume: 24 Pages: 216-222
  • Peer Reviewed
• [Journal Article] Cancer stem cell : implications in cancer biology and therapy with special reference to lung cancer (2009)
  • Author(s): Kitamura H, Okudela K, Yazawa T, Sato H, Shimoyamada H.
  • Journal Title: Lung Cancer Volume: 66 Pages: 275-281
  • Peer Reviewed
• [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 Volume: 66 Pages: 287-291
  • Peer Reviewed
• [Journal Article] Down-regulation of FXYD3 expression in human lung cancers : its mechanism and potential role in carcinogenesis (2009)
  • Author(s): Okudela K, Yazawa T, Ishii J, Woo T, Mitsui H, Bunai T, Sakaeda M, Shimoyamada H, Sato H, Tajiri M, Ogawa N, Masuda M, Sugimura H, Kitamura H.
  • Journal Title: Am J Pathol Volume: 175 Pages: 2646-2656
  • Peer Reviewed
• [Journal Article] Down-regulation of DUSP6 expression in lung cancer : its mechanism and potential role in carcinogenesis (2009)
  • Author(s): Okudela K, Yazawa T, Woo T, Sakaeda M, Ishii J, Mitsui H, Shimoyamada H, Sato H, Tajiri M, Ogawa N, Masuda M, Takahashi T, Sugimura H, Kitamura H.
  • Journal Title: Am J Pathol Volume: 175 Pages: 867-881
  • Peer Reviewed
• [Journal Article] 甲状腺腫瘍とTTF-1 (2009)
  • Author(s): 菅間博, 矢澤卓也.
  • Journal Title: 病理と臨床 Volume: 27 Pages: 460-467
  • Peer Reviewed
• [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, Shiomyamada H.
  • Journal Title: Endocr Pathol Volume: 20 Pages: 101-107
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Yazawa T, Sato H, Shimoyamada H, Okudela K, Woo T, Tajiri M, Ogura T, Ogawa N, Suzuki T, Mitsui H, Ishii J, Miyata C, Sakaeda M, Goto K, Kashiwagi K, Masuda M, Takahashi T, Kitamura H.
  • Journal Title: Am J Pathol Volume: 175 Pages: 976-987
  • 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, Yazawa T, et al.
  • Journal Title: Lung Cancer 65 Pages: 355-362
  • Peer Reviewed
• [Journal Article] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma : itsimblication in carcinogenesis (2009)
  • Author(s): Okudela K, Woo T, Yazawa T, et al.
  • Journal Title: Lung Cancer 66 Pages: 287-291
  • Peer Reviewed
• [Journal Article] Down-regulation of DUSP6 expression in lung cancer : its mechanism and potential role in carcinogenesis (2009)
  • Author(s): Okudela K, Yazawa T, et al.
  • Journal Title: American Journal of Pathology 175 Pages: 867-881
  • Peer Reviewed
• [Journal Article] Neuroendocrine cancer-specific up-regulating mechanism of insulin-like growth factor binding protein-2 in small cell lung cancer (2009)
  • Author(s): Yazawa T, Sato H, Shimoyamada H, Okudela K, et al.
  • Journal Title: American Journal of Pathology 175 Pages: 976-987
  • Peer Reviewed
• [Journal Article] Down-regulation of FXYD3 expression in human lung cancers : its mechanism and potential role in carcinogenesis (2009)
  • Author(s): Okudela K, Yazawa T, et al.
  • Journal Title: American Journal of Pathology 176 Pages: 2646-2656
  • Peer Reviewed
• [Journal Article] 甲状腺腫瘍とTTF-1 (2009)
  • Author(s): 菅間博, 矢澤卓也, 他
  • Journal Title: 病理と臨床 27 Pages: 460-467
  • Peer Reviewed
• [Journal Article] Small cell lung cancer : significance of RB alterations and TTF1 expression in its carcinogenesis, phenotype and biology (2009)
  • Author(s): Kitamura H, Yazawa T, et al.
  • Journal Title: Endocrine Pathology 20 Pages: 101-107
  • Peer Reviewed
• [Journal Article] Cancer stem cell : implications in cancer biology and therapy with special reference to lung cancer (2009)
  • Author(s): Kitamura H, Okudela K, Yazawa T, et al.
  • Journal Title: Lung Cancer 66 Pages: 275-281
  • Peer Reviewed
• [Presentation] 甲状腺癌においてTTF-1により発現変化する遺伝子の網羅的解析 (2012)
  • Author(s): 下山田博明, 大森嘉彦, 榮田昌史, 有益優, 石井順, 矢澤卓也, 菅間博
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-28
• [Presentation] 肺癌の神経/神経内分泌形質にASCL1およびRESTが与える影響の解析 (2012)
  • Author(s): 石井順, 有益優, 榮田昌史, 柏木維人, 下山田博明, 佐藤華子, 宮田千恵, 藤原正親, 菅間博, 青木一郎, 矢澤卓也
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 肺癌におけるThyroid Transcription Factor-1の発現機序に関与する因子の検索 (2012)
  • Author(s): 榮田昌史, 佐藤華子, 宮田千恵, 石井順, 有益優, 柏木維人, 下山田博明, 菅間博, 青木一郎, 矢澤卓也
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-27
• [Presentation] 「神経内分泌腫瘍の病理診断最近の進歩」神経内分泌癌の形質を制御する転写因子についての機能解析 (2011)
  • Author(s): 矢澤卓也
  • Organizer: 第15回日本内分泌病理学会学術総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-10-24
• [Presentation] 「神経内分泌腫瘍の病理診断最近の進歩」神経内分泌癌の形質を制御する転写因子についての機能解析 (2011)
  • Author(s): 矢澤卓也
  • Organizer: 第15回日本内分泌病理学会学術総会シンポジウム
  • Place of Presentation: 都道府県会館(東京都)
  • Year and Date: 2011-10-24
• [Presentation] 神経内分泌マーカー発現に対するNeuroD, ASCL1の関与について (2011)
  • Author(s): 柏木維人, 石井順, 榮田昌史, 有益優, 佐藤華子, 奥寺康司, 下山田博明, 矢澤卓也
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-28
• [Presentation] 神経内分泌マーカー発現に対するNeuroD, ASCL1の関与について (2011)
  • Author(s): 柏木維人, 石井順, 榮田昌史, 有益優, 佐藤華子, 奥寺康司, 下山田博明, 矢澤卓也
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-04-28
• [Presentation] An altered histological sub-typing system for lung adenocarcinoma (2010)
  • Author(s): 奥寺康司, .哲漢, 三井秀昭, 矢澤卓也, 下山田博明, 田尻道彦, 小川伸郎, 益田宗孝, 北村均
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-28
• [Presentation] IGFBP-4 expression deficiency by epigenetic silencing in non-small cell lung cancers (2010)
  • Author(s): 佐藤華子, 榮田昌史, 石井順, 柏木維人, 奥寺康司, 下山田博明, 北村均, 矢澤卓也
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-28
• [Presentation] 肺癌細胞におけるNeuroD発現はNeural Cell Adhesion Molecule 1(NCAM1)を誘導する (2010)
  • Author(s): 柏木維人, 石井順, 榮田昌史, 佐藤華子, 奥寺康司, 下山田博明, 北村均, 矢澤卓也
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-04-28
• [Presentation] 肺癌細胞におけるNeuroD発現はNeural Cell Adhesion Molecule 1(NCAM1)を誘導する (2010)
  • Author(s): 柏木維人(矢澤卓也)
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京,京王プラザホテル
  • Year and Date: 2010-04-28
• [Presentation] IGFBP-4 expressio deficiency by epigenetic silencing in non-small cell lung cancers (2010)
  • Author(s): 佐藤華子(矢澤卓也)
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京,京王プラザホテル
  • Year and Date: 2010-04-28
• [Presentation] An altered histological sub-typing system for lung adenocarcinoma (2010)
  • Author(s): 奥寺康司(矢澤卓也)
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 東京,京王プラザホテル
  • Year and Date: 2010-04-28
• [Presentation] がん細胞の異型性の分子基盤(イオンチャンネル制御因子FXYD3の関与) (2009)
  • Author(s): 奥寺康司, 矢澤卓也, 下山田博明, .哲漢, 佐藤華子, 竹内智康, 石井順, 榮田昌史, 後藤和哉, 宮田千恵, 柏木維人, 椙村春彦, 北村均
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-02
• [Presentation] 癌におけるインスリン様増殖因子結合蛋白-2(IGFBP-2)およびIGFBP-4の発現現弱機構の解析 (2009)
  • Author(s): 佐藤華子, 矢澤卓也, 下山田博明, 奥寺康司, 榮田昌史, 石井順, 宮田千恵, 後藤和哉, 柏木維人, 北村均
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-02
• [Presentation] ヒト肺腺癌におけるVEGF-Aの発現機序におけるNAB2, egr-1の役割の解明 (2009)
  • Author(s): 下山田博明, 矢澤卓也, 佐藤華子, 奥寺康司, 宮田千恵, 榮田昌史, 石井順, 後藤和哉, 柏木維人, 北村均
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-02
• [Presentation] 肺腺癌におけるTTF-1遺伝子プロモーターのメチル化解析 (2009)
  • Author(s): 矢澤卓也, 佐藤華子, 宮田千恵, 下山田博明, 奥寺康司, 石井順, 榮田昌史, 後藤和哉, 柏木維人, 北村均
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-05-02