The molecular basis of morphological atypism (proteome analysis of KRAS downstream factors)

• Project/Area Number: 23590428
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Yokohama City University
• Principal Investigator: OKUDELA KOJI 横浜市立大学, 医学部, 講師 (10326027)
• Co-Investigator(Kenkyū-buntansha): KATAYA Akira 日本医科大学, 医学部, 助教 (10333113) ; NAGAHARA Noriyuki 日本医科大学, 医学部, 准教授 (10208043) ; WOO Tetsukan 横浜市立大学, 医学研究科, 共同研究員 (90537177) ; YAZAWA Takuya 杏林大学, 医学部, 准教授 (50251054) ; SHIMOYAMADA Hiroaki 杏林大学, 医学部, 助教 (60381472)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: atypism / lung cancer / 肺癌 / 異型性 / CLIC4

Research Abstract

A purpose of present study is to elucidate a molecular basis of morphological atypism. This study investigated the proteome modulated by oncogenic KRAS in immortalized airway epithelial cells. We here focused on CLIC4 to investigate its potential involvement in an induction of the morphologic atypism in lung cancers. CILC4 protein levels were reduced in some lung cancer cell lines. The knockdown of CLIC4 in an immortalized airway cell line modulated a cell shape as marked enlargement of cells and nuclei. CLIC4 protein levels tended to be lower in high-grade tumors. These results suggest that the alteration in CLIC4 could induce some morphological atypism of neoplastic cells and could be involved in carcinogenesis of the lung.

Research Products

• [Journal Article] Two cases of pulmonary sarcoidosis presenting with subpleural reticular shadows in the lower lobes (2014)
  • Author(s): Sekine A, Takemura T, Baba T, Oda T, Iwasawa T, Okudela K, Ogura T
  • Journal Title: Intern Med Volume: 53 Pages: 455-460
  • Peer Reviewed
• [Journal Article] Establishment of successively transplantable rabbit VX2 cancer cells that express enhanced green fluorescent protein (2014)
  • Author(s): Oshiro H, Fukumura H, Nagahama K, Sato I, Sugiura K, Iobe H, Okiyama E, Nagao T, Nagashima Y, Aoki I, Yamanaka S, Murakami A, Maegawa J, Chishima T, Ichikawa Y, Ishikawa Y, Nagai T, Nomura M, Ohashi K, Okudela K
  • Journal Title: Med Mol Morphol Volume: 47 Issue: 3 Pages: 130-136
  • DOI: 10.1007/s00795-013-0052-x
  • Peer Reviewed
• [Journal Article] Proteome Analysis for Downstream Targets of Oncogenic KRAS - the Potential Participation of CLIC4 in Carcinogenesis in the Lung (2014)
  • Author(s): Okudela K, Katayama A, Woo T, Mitsui H, Suzuki T, Tateishi Y, Umeda S, Tajiri M, Masuda M, Nagahara N, Kitamura H, Ohashi K
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed
• [Journal Article] Diffuse alveolar hemorrhage as a fatal adverse effect of bevacizumab : an autopsy case (2014)
  • Author(s): Ikeda S, Sekine A, Kato T, Yoshida M, Ogata R, Baba T, Nagahama K, Okudela K, Ogura T
  • Journal Title: Jpn J Clin Oncol Volume: 44 Pages: 497-500
  • Peer Reviewed
• [Journal Article] Lung abscess combined with chronic osteomyelitis of the mandible successfully treated with video-assisted thoracoscopic surgery (2014)
  • Author(s): Arai H, Inui K, Watanabe K, Watanuki K, Okudela K, Tsuboi M, Masuda M
  • Journal Title: Clin Respir J
  • Peer Reviewed
• [Journal Article] Establishment of successively transplantable rabbit VX2 cancer cells that express enhanced green fluorescent protein (2014)
  • Author(s): Oshiro H, Fukumura H, Nagahama K, Sato I, Sugiura K, Iobe H, Okiyama E, Nagao T, Nagashima Y, Aoki I, Yamanaka S, Murakami A, Maegawa J, Chishima T, Ichikawa Y, Ishikawa Y, Nagai T, Nomura M, Ohashi K and Okudela K
  • Journal Title: Med Mol Morphol Volume: 印刷中 Issue: 1 Pages: 13-23
  • DOI: 10.1007/s00795-014-0071-2
  • Peer Reviewed / Open Access
• [Journal Article] Expression of HDAC9 in lung cancer-potential role in lung carcinogenesis. Int J Clin Exp Pathol 7: 213-220. (2014)
  • Author(s): Okudela K, Mitsui H, Suzuki T, Woo T, Tateishi Y, Umeda S, Saito Y, Tajiri M, Masuda M and Ohashi K
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 213-220
  • Peer Reviewed
• [Journal Article] Diffuse alveolar hemorrhage as a fatal adverse effect of bevacizumab (2014)
  • Author(s): Ikeda S, Sekine A, Kato T, Yoshida M, Ogata R, Baba T, Nagahama K, Okudela K and Ogura T
  • Journal Title: Jpn J Clin Oncol Volume: 44 Issue: 5 Pages: 497-500
  • DOI: 10.1093/jjco/hyu023
  • Peer Reviewed
• [Journal Article] Proteome analysis for downstream targets of oncogenic KRAS--the potential participation of CLIC4 in carcinogenesis in the lung. (2014)
  • Author(s): Okudela K, Katayama A, Woo T, Mitsui H, Suzuki T, Tateishi Y, Umeda S, Tajiri M, Masuda M, Nagahara N, Kitamura H and Ohashi K
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: 1-10
  • DOI: 10.1371/journal.pone.0087193
  • Peer Reviewed / Open Access
• [Journal Article] Lung abscess combined with chronic osteomyelitis of the mandible successfully treated with video-assisted thoracoscopic surgery (2014)
  • Author(s): Arai H, Inui K, Watanabe K, Watanuki K, Okudela K, Tsuboi M and Masuda M
  • Journal Title: Clin Respir J Volume: 印刷中 Issue: 2 Pages: 253-256
  • DOI: 10.1111/crj.12115
  • Peer Reviewed
• [Journal Article] Hepatocyte nuclear factor-1 alpha inactivated hepatocellular adenomas in patient with congenital absence of the portal vein : a case report (2013)
  • Author(s): Tateishi Y, Furuya M, Kondo F, Torii I, Nojiri K, Tanaka Y, Umeda S, Okudela K, Inayama Y, Endo I, Ohashi K
  • Journal Title: Pathol Int Volume: 63 Pages: 358-363
  • Peer Reviewed
• [Journal Article] Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance (2013)
  • Author(s): Okudela K, Woo T, Mitsui H, Suzuki T, Tajiri M, Sakuma Y, Miyagi Y, Tateishi Y, Umeda S, Masuda M, Ohashi K
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Expression of HDAC9 in lung cancer - potential role in lung carcinogenesis (2013)
  • Author(s): Okudela K, Mitsui H, Suzuki T, Woo T, Tateishi Y, Umeda S, Saito Y, Tajiri M, Masuda M, Ohashi K
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 213-220
  • Peer Reviewed
• [Journal Article] An association between nuclear morphology and immunohistochemical expression of p53 and p16INK4A in lung cancer cells (2013)
  • Author(s): Okudela K
  • Journal Title: Med Mol Morphol
  • Peer Reviewed
• [Journal Article] Unique mutation, accelerated mTOR signaling and angiogenesis in the pulmonary cysts of Birt-Hogg-Dube syndrome (2013)
  • Author(s): Nishii T, Tanabe M, Tanaka R, Matsuzawa T, Okudela K, Nozawa A, Nakatani Y and Furuya M
  • Journal Title: Pathol Int Volume: 63 Pages: 45-55
  • Peer Reviewed
• [Journal Article] Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies (2013)
  • Author(s): Arai H, Okudela K, Oshiro H, Komitsu N, Mitsui H, Nishii T, Tsuboi M, Nozawa A, Noishiki Y, Ohashi K, Inui K, Masuda M
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 395-410
  • Peer Reviewed
• [Journal Article] Hepatocyte Nuclear Factor-1ΑInactivated Hepato- cellular Adenomas in Patient With Congenital Absence of The Portal Vein (2013)
  • Author(s): Tateishi Y, Furuya M, Kondo F, Okudela K, Umeda S, Ohashi K
  • Journal Title: Pathol Int Volume: vol 63 Issue: 7 Pages: 358-363
  • DOI: 10.1111/pin.12072
  • Peer Reviewed
• [Journal Article] Downregulation of ALDH1A1 expression in non-small cell lung carcinomas - its clinicopathologic and biological significance (2013)
  • Author(s): Okudela K, Woo T, Mitsui H, Suzuki T, Tajiri M, et al.
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases (2013)
  • Author(s): Woo T, Okudela K, Mitsui H, Tajiri M, Yamamoto T, et al.
  • Journal Title: Pathol Int Volume: 62 Issue: 12 Pages: 785-791
  • DOI: 10.1111/pin.12016
  • Peer Reviewed
• [Journal Article] Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases (2012)
  • Author(s): Woo T, Okudela K, Mitsui H, Tajiri M, Yamamoto T, Rino Y, Ohashi K, Masuda M
  • Journal Title: Pathol Int Volume: 62 Pages: 785-791
  • Peer Reviewed
• [Journal Article] Expression of the potential cancer stem cell markers, CD133, CD44, ALDH1, and beta-catenin, in primary lung adenocarcinoma--their prognostic significance (2012)
  • Author(s): Okudela K, Woo T, Mitsui H, Tajiri M, Masuda M, Ohashi K
  • Journal Title: Pathol Int Volume: 62 Pages: 792-801
  • Peer Reviewed
• [Journal Article] Identification of miR-30d as a novel prognostic maker of prostate (2012)
  • Author(s): Kobayashi N, Uemura H, Nagahama K, Okudela K, Furuya M, Ino Y, Ito Y, Hirano H, Inayama Y, Aoki I, Nagashima Y, Kubota Y, Ishiguro H
  • Journal Title: Oncotarget Volume: 3 Pages: 1455-71
  • Peer Reviewed
• [Journal Article] Pulmonary adenocarcinoma, Lambert--Eaton myasthenic syndrome, and voltage-gated calcium channels : a case report (2012)
  • Author(s): Arai H, Inui K, Hashimoto K, Kan OK, Nishii T, Kishida H, Okudela K, Nozawa A, Kaneko T, Masuda M
  • Journal Title: J Med Case Rep Volume: 6 Pages: 281-281
  • Peer Reviewed
• [Journal Article] Expression of the potential cancer stem cell markers, CD133, CD44, ALDH1, and beta-catenin, in primary lung adenocarcinoma-their prognostic significance (2012)
  • Author(s): Okudela K, Woo T, Mitsui H, Tajiri M, Masuda M, et al.
  • Journal Title: Pathol Int Volume: 62 Issue: 12 Pages: 792-801
  • DOI: 10.1111/pin.12019
  • Peer Reviewed
• [Journal Article] Severe obliterative bronchitis associated with Stevens-Johnson syndrome (2011)
  • Author(s): Woo T, Saito H, Yamakawa Y, Komatsu S, Onuma S, Okudela K, Nozawa A, Aihara M, Ikezawa Z, Ishigatsubo Y
  • Journal Title: Intern Med Volume: 50 Pages: 2823-2827
  • Peer Reviewed
• [Journal Article] The morphologic atypism of epithelial neoplasms; its molecular basis and pathologic significance (2011)
  • Author(s): Okudela-K
  • Journal Title: 横浜医学 Volume: 62 Pages: 51-68
  • Peer Reviewed
• [Presentation] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma (2014)
  • Author(s): 奥寺康司, 他
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島
  • Year and Date: 2014-04-25
• [Presentation] Proteome analysis for downstream targets of KRAS - CLIC4 in lung carcinogenesis - (2014)
  • Author(s): 奥寺康司、立石陽子、梅田茂明、三井秀昭、鈴木健久、禹哲漢、田尻道彦、大橋健一
  • Organizer: 第１０３回 日本病理学会総会
  • Place of Presentation: 広島国際会議場（広島）
• [Presentation] 肺癌の発生・進展におけるKRAS-miR-31経路の意義 (2013)
  • Author(s): 奥寺康司、立石陽子、梅田茂明、三井秀昭、鈴木健久、禹哲漢、田尻道彦、大橋健一
  • Organizer: 第１０２回 日本病理学会総会
  • Place of Presentation: 札幌文芸館（札幌）
• [Presentation] Proteome Analysis for Downstream Targets of Oncogenic KRAS - the Potential Participation of CLIC4 in Carcinogenesis in the Lung (2012)
  • Author(s): 奥寺康司, 他
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-04-26
• [Presentation] 気管支の上皮筋肉上皮腫の一例 (2011)
  • Author(s): 奥寺康司、矢澤卓也、田尻道彦、下山田博明、北村均
  • Organizer: 日本病理学会総会（第１００回）
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Significant association between EGFR-mutated lung adenocarcinoma and past illness from gastric cancer or uterine myoma
  • Author(s): 奥寺康司他
  • Organizer: 第１０１回 日本病理学会総会
  • Place of Presentation: 京王プラザホテル（東京）
  • Invited
• [Book] 呼吸と循環 「肺癌個別化治療におけるバイオマーカー」 (2012)
  • Author(s): 奥寺 康司、瀧川 奈義夫、岡本 邦男、間野 博行、清水 哲男
  • Total Pages: 5
  • Publisher: 医学書院
• [Book] Cancer Stem Cells Theories and Practice (2011)
  • Author(s): Koji Okudela, Noriyuki Nagahara, Akira Katayama, Hitoshi Kitamura
  • Publisher: InTech. Publication