Exploration of the genes that repress indefinite proliferation of lung cancer cells

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: HIYAMA Keiko Hiroshima University, 原爆放射線医科学研究所, 准教授 (60253069)
• Project Period (FY): 2007 – 2008
• Keywords: 肺癌 / 不死化 / 分子標的 / テロメラーゼ / 抗癌剤 / 気道上皮 / 幹細胞

Research Abstract

肺癌細胞株の網羅的発現解析により、肺癌の無限増殖を抑制する新たな分子標的候補を絞り込むと同時に、遺伝子導入により、その評価に有用な正常と不死化がん細胞の中間に位置すると考えられる気道上皮細胞を樹立した。これらは癌幹細胞にも有効な無限増殖を抑制する新たな抗癌剤の開発への展開が期待された。さらに、p16/RB経路の不活化のないテロメラーゼ活性化が幹細胞に由来する肺癌のマーカーである可能性を示した。

Research Products

• [Journal Article] Detection of CpG island hypermethylation of caspase-8 in neuroblastoma using an oligonucleotide array (2009)
  • Author(s): Kamimatsuse A, Matsuura K, Moriya S, Fukuba I, Yamaoka H, Fukuda E, Kamei N, Hiyama K, Sueda T, Hiyama E
  • Journal Title: Pediatr Blood Cancer 52 Pages: 777-783
  • Peer Reviewed
• [Journal Article] EMP3 as a tumor suppressor gene for esophageal squamous cell carcinoma (2009)
  • Author(s): Fumoto S, Hiyama K, Tanimoto K, Noguchi T, Hihara J, Hiyama E, Noguchi T, Nishiyama M
  • Journal Title: Cancer Letters 274 Pages: 25-32
  • Peer Reviewed
• [Journal Article] Human mismatch repair gene, MLH1, is transcriptionally repressed by the hypoxia-inducible transcription factors (2008)
  • Author(s): Nakamura H, Tanimoto K, Hiyama K, Yunokawa M, Kawamoto T, Kato Y, Yoshiga K, Poellinger L, Hiyama E, Nishiyama M.
  • Journal Title: DEC1 and DEC2. Oncogene 27 Pages: 4200-4209
  • Peer Reviewed
• [Journal Article] Exploration of the genes responsible for unlimited proliferation of immortalized lung fibroblasts (2008)
  • Author(s): Hiyama K, Tanimoto K, Nishimura Y, Tsugane M, Fukuba I, Sotomaru Y, Hiyama E, Nishiyama M
  • Journal Title: Exp Lung Res 34 Pages: 373-390
  • Peer Reviewed
• [Journal Article] Differential regulation of DEC2 among hypoxia-inducible genes in endometrial carcinomas (2007)
  • Author(s): Yunokawa M, Tanimoto K, Nakamura H, Nagai N, Kudo Y, Kawamoto T, Kato Y, Hiyama E, Hiyama K, Nishiyama M
  • Journal Title: Oncol Rep 17 Pages: 871-878
  • Peer Reviewed
• [Journal Article] EGFR activating aberration occurs independently of other genetic aberrations or telomerase activation in adenocarcinoma of the lung (2007)
  • Author(s): Arifin M, Hiyama K, Tanimoto K, Wiyono WH, Hiyama E, Nishiyama M
  • Journal Title: Oncol Rep 17 Pages: 1405-1411
  • Peer Reviewed
• [Journal Article] Selection of a novel drug-response predictor in esophageal cancer : a novel screening method using microarray and identification of IFITM1 as a potent marker gene of CDDP response (2007)
  • Author(s): Fumoto S, Shimokuni T, Tanimoto K, Hiyama K, Otani K, Ohtaki M, Hihara J, Yoshida K, Hiyama E, Noguchi T, Nishiyama M
  • Journal Title: Int J Oncol 32 Pages: 413-423
  • Peer Reviewed
• [Journal Article] Telomere and telomerase in stem cells (2007)
  • Author(s): Hiyama E, Hiyama K
  • Journal Title: Br J Cancer 96 Pages: 1020-1024
  • Peer Reviewed
• [Journal Article] A mathematical model for affymetrix genechip probe level data (2007)
  • Author(s): Otani K, Hiyama K, Satoh K, Shimamoto T, Mohamad D, Ando M, Tonda T, Kohda M, Okazaki Y, Nishiyama M, Hiyama E, Ohtaki M
  • Journal Title: JP Journal of Biostatics 1 Pages: 283-306
  • Peer Reviewed
• [Journal Article] EMP3 as a candidate tumor suppressor gene for solid tumors
  • Author(s): Fumoto S, Tanimoto K, Hiyama E, Noguchi T, Nishiyama M, Hiyama K
  • Journal Title: Expert Opinion On Therapeutic Targets (in press)
  • Peer Reviewed
• [Presentation] A new concept of carcinogenesis (2009)
  • Author(s): Hiyama K, Tanimoto K
  • Organizer: Symposium in University of Andalas
  • Place of Presentation: Padang, Indonesia
  • Year and Date: 2009-02-16
• [Presentation] Oncogenic addiction in lung cancer. Plenary Symposium (2009)
  • Author(s): Hiyama K, Arifin M, Hiyama E
  • Organizer: The 7^<th> Scientific Respiratory Medicine Meeting PIPKRA2009
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2009-02-15
• [Presentation] Hypoxic signaling in cancers. Plenary Symposium (2009)
  • Author(s): Tanimo K, Hiyama K
  • Organizer: The 7^<th> Scientific Respiratory Medicine Meeting PIPKRA2009
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2009-02-15
• [Presentation] Interstitial Lung Diseases (ILD) update. Plenary Symposium (2009)
  • Author(s): Hiyama K, Arifin M, Tanimoto K
  • Organizer: The 7^<th> Scientific Respiratory Medicine Meeting PIPKRA2009
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2009-02-14
• [Presentation] Diagnostic factors in cancers. Satellite Symposium (2009)
  • Author(s): Tanimoto K, Hiyama K
  • Organizer: The 7^<th>Scientific Respiratory Medicine Meeting PIPKRA2009
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2009-02-14
• [Presentation] Molecular basics of lung cancer. Workshop (2009)
  • Author(s): Hiyama K, Tanimoto K, Hiyama E
  • Organizer: The 7^<th> Scientific Respiratory Medicine Meeting PIPKRA2009
  • Place of Presentation: Jakarta, Indonesia
  • Year and Date: 2009-02-13
• [Presentation] Exploration of the genes associated with chemosensitivity and indefinite proliferation of lung cancer cells (2008)
  • Author(s): Hiyama K, Arifin M, Tanimoto K, Otani k, Ohtaki M, Hiyama E, Nishiyama M
  • Organizer: The 13^<th> Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2008-11-20
• [Presentation] Telomere shortening and genetic variations in telomerase components and metabolic enzymes in Japanese patients with COPD (2008)
  • Author(s): Arifin M, Tanimoto K, Budhi A, Hiyama E, Nishiyama M, Hiyama K
  • Organizer: The 13^<th> Congress of the Asian Pacific Society of Respirology
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 2008-11-20
• [Presentation] Genes commonly upregulated in immortal cancer cells are novel molecular targets for universal anti-cancer strategy (2008)
  • Author(s): Hiyama K, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: Ehrlich II- 2^<nd> World Conference on Magic Bullets
  • Place of Presentation: Nurnberg, Germany
  • Year and Date: 2008-10-04
• [Presentation] Effectiveness and complications of treatment childhood liver tumors-from the experience of JPLT(Japanese Study Group for Pediatric Liver Tumor) (2008)
  • Author(s): Hiyama E, Yamaoka H, Nishimura S, Hishiki T, Hiyama K, Sasaki F, Horie E, Ohnuma N
  • Organizer: Ehrlich II- 2^<nd> World Conference on Magic Bullets
  • Place of Presentation: Nurnberg, Germany
  • Year and Date: 2008-10-04
• [Presentation] Telomere shortening and TERT/TERC genetic variations in patients with collagen diseases (2008)
  • Author(s): Hiyama K, Arifin M, Uchida A, Ozawa Y, Tanimoto K., Hirai Y, Yamanishi Y, Hiyama E, Nishiyama M
  • Organizer: Annual European Congress of Rheumatology
  • Place of Presentation: Paris, France
  • Year and Date: 2008-06-11
• [Presentation] EMP3 may be a tumor suppressor gene in late stage of neuroblastoma development (2008)
  • Author(s): Fukuba I, Hiyama K, Kamimatsuse A, Yamaoka H, Fukuda E, Tazaki T, Hiyama E
  • Organizer: Advances in Neuroblastma Research 2008(ANR)
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2008-05-22
• [Presentation] High-Resolution mapping of single nucleotide polymorphisms and DNA methylation in human nueroblastoma using oligonucleotide microarray (2008)
  • Author(s): Hiyama E, Yamaoka H, Fukuba I, Fukuda E, Kamimatsuse A, Kamei N, Onitake Y, Hiyama K, Sueda T
  • Organizer: Advances in Neuroblastma Research 2008(ANR)
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2008-05-22
• [Presentation] Identification of candidate genes involving in Neuroblastoma Using a New Mathematical model for genechip data (2008)
  • Author(s): Kamei N, Hiyama E, Otani K, Hiyama K, Kamimatsuse A, Yamaoka H, Ohtaki M
  • Organizer: Advances in Neuroblastma Research 2008(ANR)
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2008-05-22
• [Presentation] HIF-1-DEC pathway regulates expressions of DNA repair genes (2008)
  • Author(s): Tanimoto K, Nakamura H, Fumoto S, Hiyama E, Yoshiga K, Eguchi H, Nishiyama M, Hiyama K
  • Organizer: Annual Meeting of Am. Assoc. Cancer Res 2008
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2008-04-14
• [Presentation] EMP3, as a candidate of tumor suppressor gene for esophageal squamous cell carcinoma(ESCC) (2008)
  • Author(s): Fumoto S, Tanimoto K, Arifin M, Noguchi T, Noguchi T, Hiyama E, Eguchi H, Nishiyama M, Hiyama K
  • Organizer: Annual Meeting of Am. Assoc. Cancer Res 2008
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2008-04-14
• [Presentation] Possible mechanism of lung adenocarcinoma development from telomerase-positive "stem cells"free from cellular senescence. The Fifth International Symposium of 21^<st> Century COE Program (2008)
  • Author(s): Arifin M, Hiyama K, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: Hiroshima University Radiation Casualty Medical Research Center
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2008-01-23
• [Presentation] EMP3 may be a tumor suppressor gene in late stage of neuroblastoma development. The Fifth International Symposium of 21^<st> Century COE Program (2008)
  • Author(s): Fukuba I, Hiyama K, Kamimatsuse A, Tazaki T, Yamaoka H, Fukuda E, Arifin M, Fumoto S, Tanimoto K, Nishiyama M, Hiyama E
  • Organizer: Hiroshima University Radiation Casualty Medical Research Center
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2008-01-23
• [Presentation] Novel hypoxia inducible genes as molecular targets for anti-cancer therapy (2008)
  • Author(s): Tanimoto K, Nakamura H, Fumoto S, Hiyama E, Yoshiga K, Eguchi H, Nishiyama M, Hiyama K
  • Organizer: The 5^<th> International Symposium of Hiroshima University 21th Century COE Program, Radiation Casualty Medical Research Center
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2008-01-19
• [Presentation] Hypoxia-inducible transcription factors, DEC1 and DEC2, suppress expressions of DNA repair genes in cancer cells (2008)
  • Author(s): Tanimoto K, Nakamura H, Hiyama E, Nishiyama M, Hiyama K
  • Organizer: Keystone Symposia on Molecular and Cellular Biology
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2008-01-19
• [Presentation] Development of Telomerase-Positive Lung Adenocarcinomas without Inactivation of p16/Rb Pathway (2007)
  • Author(s): Hiyama K, Arifin M, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: The Role of Telomeres and Telomerase in Cancer Research
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2007-12-07
• [Presentation] Immortalization and cancer formation of human mesenchymal stem cells (2007)
  • Author(s): Hiyama E, Onitake Y, Fukuba I, Fukuda E, Sudo T, Sueda T, Sotomaru Y, Hiyama K
  • Organizer: The Role of Telomeres and Telomerase in Cancer Research
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2007-12-07
• [Presentation] Inactimation of P16/RB pathway is not a prerequisite for half of lung adenocarcinoma with high telomerase activity (2007)
  • Author(s): Arifin M, Hiyama K, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: The 15^<th> Anniversary of Hiroshima Cancer Seminar Foundation. The 17^<th> Internatl. Symposium. "Radiation Therapy for Cancer"
  • Place of Presentation: Hiroshima, Japan
  • Year and Date: 2007-11-11
• [Presentation] Pharmacogenomic (PG) analysis for prediction of individual response to paclitaxel in 5-FU-refractory metastatic gastric cancer : Prediction formula of tumor response using novel marker genes and genotypes associated with the toxicity (2007)
  • Author(s): Ikeda R, Yoshida K, Takagane A, Tsuburaya A, Kobayashi O, Sunouchi H, Matsukawa M, Tanimoto K, Hiyama K, Nishiyama M
  • Organizer: 43^<rd> Annual Meeting of Am. Soc. Clin. Oncol.
  • Place of Presentation: Chicago, IL, USA
  • Year and Date: 2007-06-03
• [Presentation] POT1 transfection may cause shortening of telomere 3-overhang increasing chemoresistance and alternative lengthening of telomeres in cancer cell (2007)
  • Author(s): Hiyama K, Nishimura Y, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: Cold Spring Harbor Laboratory meeting on Telomeres & Telomerase
  • Place of Presentation: New York, USA
  • Year and Date: 2007-05-03
• [Presentation] Role of telomere and telomerase in human mesenchymal stem cells (2007)
  • Author(s): Hiyama E, Onitake T, Fukuba I, Fukuda E, Sudo T, Sueda T, Hiyama K
  • Organizer: Cold Spring Harbor Laboratory meeting on Telomeres & Telomerase
  • Place of Presentation: New York, USA
  • Year and Date: 2007-05-03
• [Presentation] Genome-wide single nucleotide polymorphism microarray mapping for prediction of outcome of neuroblastoma patients (2007)
  • Author(s): Hiyama E, Hiyama K, Yamaoka H, Nishiyama M., Reynolds CP, Sueda T
  • Organizer: 98^<th> Annual Meeting of Am. Assoc. Cancer Res.
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-16
• [Presentation] Exploring genes that regulate cellular proliferation and immortalization of human somatic cells (2007)
  • Author(s): Hiyama K, Tanimoto K, Hiyama E, Nishiyama M
  • Organizer: 98^<th> Annual Meeting of Am. Assoc. Cancer Res.
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-15
• [Presentation] Mechanisms of transcriptional regulation of DNA repair genes under hypoxic conditions (2007)
  • Author(s): Tanimoto K, Nakamura H, Yoshiga K, Hiyama E, Hiyama K, Nishiyama M
  • Organizer: 98^<th> Annual Meeting of Am. Assoc. Cancer Res.
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-15
• [Presentation] Interferon induced transmembrane protein 1 (IFITM1) gene is a novel candidate as a CDDP sensitivity marker in esophageal squamous cell carcinoma (ESCC) (2007)
  • Author(s): Fumoto S, Shimokuni T, Tanimoto K, Hiyama K, Noguchi T, Kawahara K, Otani K, Ohtaki M, Hiyama E, Nishiyama M
  • Organizer: 98^<th> Annual Meeting of Am. Assoc. Cancer Res.
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2007-04-15
• [Book] Telomeres and Telomerase in Cancer (2009)
  • Author(s): Hiyama K ed.
  • Total Pages: 380
  • Publisher: Humana Press, Springer, New York, NY
• [Book] Telomere and telomerase for the regulation of stem cells(Rajasekhar VK, Vemuri MC(eds.), "Regulatory Networks in Stem Cells") (2009)
  • Author(s): Hiyama E, Hiyama K.
  • Total Pages: 123-133
  • Publisher: Humana Press, Springer, New York, NY
• [Book] Clinical application of molecular diagnosis in cancer, radiation effect, and human diseases
  • Author(s): Hiyama E and Hiyama K eds.
  • Publisher: Research Signpost, Kerala, India(in press)
• [Remarks] 食道正常上皮・癌細胞のマイクロアレイプロファイルデータベース登録 : GEO GES9982 2007.12.19.
  • URL: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9982
• [Remarks] 不死化肺線維芽細胞のマイクロアレイプロファイルデータベース登録 : GEO GES9077 2007.9.18
  • URL: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9077
• [Patent(Industrial Property Rights)] イリノテカンの感受性判定方法及びその利用 (2009)
  • Inventor(s): 西山正彦、檜山桂子、谷本圭司
  • Industrial Property Rights Holder: 学校法人埼玉医科大学
  • Industrial Property Number: 2009-061455
  • Filing Date: 2009-03-13
• [Patent(Industrial Property Rights)] 食道癌の予後診断マーカー遺伝子およびその利用 (2007)
  • Inventor(s): 西山正彦、檜山桂子、谷本圭司
  • Industrial Property Rights Holder: 国立大学法人広島大学
  • Industrial Property Number: 2007-2086532007-208653
  • Filing Date: 2007-08-09
• [Patent(Industrial Property Rights)] ヒトがん細胞の不死化に関わる遺伝子およびその利用 (2007)
  • Inventor(s): 西山正彦、檜山桂子、谷本圭司、増子尋郎
  • Industrial Property Rights Holder: 国立大学法人広島大学、大鵬薬品工業株式会社
  • Industrial Property Number: WO2007/142336 A1
  • Filing Date: 2007-06-08
  • Overseas