K-ras mutation promotes colorectal carcinogenesis through GST-π

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokushima
• Principal Investigator: TAKAYAMA Tetsuji 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (10284994)
• Co-Investigator(Kenkyū-buntansha): OKAMURA Seisuke 徳島大学, 大学院・ヘルスバイオサイエンス 研究部, 助教 (30274210) ; KAJI Masako 徳島大学, 大学院・ヘルスバイオサイエンス 研究部, 助教 (30518220)
• Project Period (FY): 2010 – 2012
• Keywords: 下部消化管学(小腸、大腸)

Research Abstract

We investigated the role of GST-πin growth promotion and apoptosis resistance of colorectal cancer. When a mutated K-ras gene was transfected into K-ras wild colon cancer cell line, GST-πexpression was induced. The transfectant cells showed enhanced growth promotion activity via RAF/MEK/ERK activation and apoptosis resistance by inhibited JNK and p53 pathway. In contrast, GST-πknockdown cells showed growth inhibition and apoptosis enhancement by the inverse action mechanisms. Immunoprecipitation revealed that GST-πwas directly interacted with RAF and JNK respectively. These results indicate that GST-π promote cell growth via direct binding to RAF and subsequent RAF/MEK/ERK activation, and inhibit apoptosis via direct binding to JNK and subsequent p53 apoptosis pathway.

Research Products

• [Journal Article] A mechanism for abnormal angiogenesis in human radiation proctitis: analysis of expression profile for angiogenic factors (2012)
  • Author(s): Takeuchi T, Kimura T, Okamoto K, Aoyagi E, Miyamoto H, Kaji M, Takenaka H, Okamura S, Okahisa T, Takayama T
  • Journal Title: J Gastroenterol Volume: 47 Pages: 56- 64
  • DOI: DOI:10.1007/s00535-011- 0470-2
  • Peer Reviewed
• [Journal Article] Clinical benefit of high-sensitivity KRAS mutation testing in metastatic colorectal cancer treated with anti-EGFR antibody therapy (2012)
  • Author(s): Kimura T, Okamoto K, Miyamoto H, Kimura-Kaji M, Kitamura S, Takenaka H, Muguruma N, Okahisa T, Aoyagi E, Kajimoto M, Tsuji Y, Kogawa T, Tsuji A, Takayama T
  • Journal Title: Oncology Volume: 82 Pages: 298-304
  • DOI: DOI:10.1159/000336792
  • Peer Reviewed
• [Journal Article] Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps (2011)
  • Author(s): Takayama T, Nagashima H, Maeda M, Nojiri S, Hirayama M, Nakano Y, Takahashi Y, Sato Y, Sekikawa H, Mori M, Sonoda T, Kimura T, Kato J, Niitsu Y
  • Journal Title: Clin Cancer Res Volume: 17 Pages: 3803- 3811
  • DOI: DOI:10.1158/1078-0432.CCR-10-239 5.
  • Peer Reviewed
• [Journal Article] 大腸癌の予防 化学予防の面から (2010)
  • Author(s): 高山哲治、他
  • Journal Title: The GI Forefront Volume: 6巻 Pages: 32-36
• [Presentation] Chemopreventive effect of RAS inhibitor on azoxymethane-induced colorectal carcinogenesis. (2012)
  • Author(s): Tsuda M, Takayama T, et al
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌市教育文化会館(北海道).
  • Year and Date: 2012-09-19
• [Presentation] Colon cancer prevention targeting GST-pi. (2011)
  • Author(s): Takayama T, Nishita H, Niitsu Y
  • Organizer: 第70回日本癌学会.
  • Place of Presentation: 名古屋国際会議場(愛知県).
  • Year and Date: 2011-10-04
• [Remarks]
  • URL: http://pub2.db.tokushima-u.ac.jp/ERD/person/169695/profile-ja.html