Molecular mechanism of lung adenocarcinogenesis based on SFN and IGBP1

• Project/Area Number: 25293086
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: University of Tsukuba
• Principal Investigator: NOGUCHI MASAYUKI 筑波大学, 医学医療系, 教授 (00198582)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: Stratifin / IGBP1 / Lung adenocarcinoma / Carcinogenesis / lung adenocarcinoma

Outline of Final Research Achievements

Functional role of SFN and IGBP1 at early stage of malignant progression of lung adenocarcinoma has been analyzed.
We identified miRs those control the expression of IGBP1. A549 transferred with miR-34-b, miR-138, and miR-3841 was suppressed its proliferation in vitro. In vivo, tumor development or metastasis to the lung was reduced in shSFN-transfected A549 cells. We generated SFN-transgenic mice (Tg-SPC-SFN+/-) showing lung-specific expression of human SFN under the control of a tissue-specific enhancer, the SPC promoter. We found that Tg-SPC-SFN+/- mice developed lung tumors at a significantly higher rate than control mice after administration of chemical carcinogen, NNK. SFN appears to be a novel oncogene with potential as a therapeutic target.

Research Products

• [Journal Article] Dimethylarginine dimethylaminohydrolase 2 promotes tumor angiogenesis in lung adenocarcinoma. (2016)
  • Author(s): Shiozawa T,Iyama S,Toshima S,Sakata A,Usui S,Minami Y,Sato Y,Hizawa N,Noguchi M.
  • Journal Title: Virchows Archiv Volume: 468(2) Issue: 2 Pages: 179-190
  • DOI: 10.1007/s00428-015-1863-z
  • NAID: 120007135606
  • Peer Reviewed / Open Access
• [Journal Article] Stratifin accelerates progression of lung adenocarcinoma at an early stage. (2015)
  • Author(s): Shiba-Ishii A, Kim Y, Shiozawa T, Iyama S, Satomi K, Kano J, Sakashita S, Morishita Y, Noguchi M.
  • Journal Title: Molecular Cancer Volume: 14 Issue: 1 Pages: 142-142
  • DOI: 10.1186/s12943-015-0414-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression and clinical significance of genes frequently mutated in small cell lung cancers defined by whole exome/RNA sequencing (2015)
  • Author(s): Iwakawa, R., Kohno, T., Totoki, Y., Shibata, T., Tsuchihara, K., Mimaki, S., Tsuta, K., Narita, Y., Nishikawa, R., Noguchi, M., Harris, C. C., Robles, A. I., Yamaguchi, R., Imoto, S., Miyano, S., Totsuka, H., Yoshida, T., Yokota, J.
  • Journal Title: Carcinogenesis Volume: 116 Issue: 6 Pages: 145-152
  • DOI: 10.1093/carcin/bgv026
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Immunocytochemical staining for stratifin and OCIAD2 in bronchial washing specimens increases sensitivity for diagnosis of lung cancer. (2014)
  • Author(s): Itoguchi N1, Nakagawa T, Murata Y, Li D, Shiba-Ishii A, Minami Y, Noguchi M.
  • Journal Title: Cytopathology. Volume: - Issue: 6 Pages: 354-361
  • DOI: 10.1111/cyt.12220
  • Peer Reviewed / Open Access
• [Journal Article] ECT2 amplification and overexpression as a new prognostic biomarker for early-stage lung adenocarcinoma (2014)
  • Author(s): Yoshihiko Murata, Yuko Minami, Reika Iwakawa, Jun Yokota, Shingo Usui, Koji Tsuta, Kouya Shiraishi, Shingo Sakashita, Kaishi Satomi, Tatsuo Iijima and Masayuki Noguchi
  • Journal Title: Cancer Science Volume: 105 Issue: 4 Pages: 490-497
  • DOI: 10.1111/cas.12363
  • Peer Reviewed / Open Access
• [Journal Article] Diagnosis of lung adenocarcinoma in resected specimens: Implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification. (2013)
  • Author(s): Travis WD, Brambilla E, Noguchi M, et al.
  • Journal Title: Arch Pathol Lab Med Volume: 137 Pages: 685-705
  • Peer Reviewed
• [Journal Article] Diagnosis of lung adenocarcinoma in small biopsied and cytology: Implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification. (2013)
  • Author(s): Travis WD, Brambilla E, Noguchi M, et al.
  • Journal Title: Arch Pathol Lab Med Volume: 137 Pages: 688-684
  • Peer Reviewed
• [Journal Article] Interobserver agreement in the nuclear grading of primary pulmonary adenocarcinoma (2013)
  • Author(s): Nakazato Y, Maeshima MA, Noguchi M, et al.
  • Journal Title: J Thorac Oncol Volume: 8 Pages: 736-743
  • Peer Reviewed
• [Journal Article] Differences in the prognostic implications of vascular invasion between lung adenocarcinoma and squamous cell carcinoma. (2013)
  • Author(s): Usui S, Minami Y, Noguchi M, et al.
  • Journal Title: Lung Cancer Volume: 82 Pages: 407-412
  • Peer Reviewed
• [Journal Article] In cpressed lung tissue microscopic sections of adenocarcinoma in situ may mimic papillary adenocarcinoma. (2013)
  • Author(s): Thunnnissen E, Belien JA, Noguchi M, et al.
  • Journal Title: Arch Pathol Lab Med Volume: 137 Pages: 1792-1797
  • Peer Reviewed
• [Journal Article] Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer. (2013)
  • Author(s): Iwakawa R, Takenaka M, Noguchi M, et al.
  • Journal Title: Genes Chromosomes Cancer Volume: 52 Pages: 802-816
  • Peer Reviewed
• [Presentation] 新WHO分類における肺癌分類の要点と問題点 (2015)
  • Author(s): 野口 雅之
  • Organizer: 第56回日本肺癌学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県）
  • Year and Date: 2015-11-27
• [Presentation] Molecular Pathology of Alveolar Premalignancy (2015)
  • Author(s): 野口 雅之
  • Organizer: IASLC2015（the 16th IASLC World Conference on Lung Cancer）
  • Place of Presentation: Colorado Convention Center（Colorado,United States of America）
  • Year and Date: 2015-09-09
  • Int'l Joint Research / Invited
• [Presentation] The New WHO Classification of Lung Adenocarcinoma, points for diagnosis and biological significance (2015)
  • Author(s): 野口 雅之
  • Organizer: APIAP 2015： The 9th Asia Pacific IAP Congress
  • Place of Presentation: Brisbane Convention & Exhibition Centre（Brisbane , Australia）
  • Year and Date: 2015-06-06
  • Int'l Joint Research / Invited
• [Presentation] Adenocarcinoma of the lung (2015)
  • Author(s): 野口 雅之
  • Organizer: Pathology Expert Forum: The WHO Classification of Lung Tumors2015
  • Place of Presentation: GIS NTU Convention Center（Taipei、Taiwan）
  • Year and Date: 2015-05-17
  • Int'l Joint Research / Invited
• [Presentation] 「宿題報告2」肺腺癌の組織発生と悪性化の病理学 (2015)
  • Author(s): 野口 雅之
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県）
  • Year and Date: 2015-04-30
  • Invited
• [Presentation] 特別講演「Early genetic and phenotypic alterations of lung adenocarcinoma」 (2014)
  • Author(s): 野口 雅之
  • Organizer: Training of the Education Program for Pathology and Genetic Tests
  • Place of Presentation: つくば臨床検査教育・研究センター
  • Year and Date: 2014-11-10 – 2014-11-16
  • Invited
• [Presentation] Scientific program :Pulmonary pathology sessions (2014)
  • Author(s): 野口 雅之
  • Organizer: The 30th Congress of the International Academy of Pathology(IAP2014)
  • Place of Presentation: Bangkok Convention Centre at CentraｌWorld Bangkok,Thailand
  • Year and Date: 2014-10-05 – 2014-10-11
  • Invited
• [Presentation] 肺腺癌の悪性度因子としてのOCIAD2の臨床病理学的意義
  • Author(s): 糸口直江、佐藤泰樹、永田千草、南優子、野口雅之
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌
• [Presentation] 進行肺腺癌におけるIGBP1の異常発現の解析
  • Author(s): 佐藤泰樹、坂下信悟、南優子、野口雅之
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌
• [Presentation] ECT2の遺伝子異常は早期肺腺癌における新規予後マーカーである
  • Author(s): 村田佳彦、南優子、岩川麗香、横田淳、野口雅之
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Book] WHO Classification of Tumours,Vol.7 (2015)
  • Author(s): W.D.Travis,E.Brambilla, A.P.Burke,A.Marx,A.G.Nicholson,Noguchi M.
  • Total Pages: 412
  • Publisher: WORLD HEALTH ORGANIZATION:Lyon,France
• [Book] CLASSIC ANATOMIC PATHOLOGY AND LUNG CANCER. (2014)
  • Author(s): Ignacio I，Wistuba，Elisabeth Brambilla，M Noguchi
  • Total Pages: 24
  • Publisher: The IASLC Multidisciplinary Approach to Thoracic Oncology．