Elucidation of Field Effect in Colorectal Cancer with Mutant KRAS
| Project/Area Number |
24501322
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
NABESHIMA Kazuki 福岡大学医学部, 病理学, 教授 (40189189)
KAWADA Kenji 京都大学医学部, 消化管外科, 講師 (90322651)
SHIRASAWA Senji 福岡大学医学部, 細胞生物学, 教授 (10253535)
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| Research Collaborator |
OTA Yasuharu
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | KRAS / ３次元培養 / 大腸癌 / 3次元培養 / 微小環境 / 薬剤スクリーニング / フィールドエフェクト / 大腸がん |
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| Outline of Final Research Achievements |
We have previously compared HKe3 cells, derived from colorectal cancer HCT116 cells and disrupted at mutated (mt) KRAS gene, with HCT116 cells in the 3D matrigel culture and found mtKRAS involvement in the inhibition of gene expressions associated with normal morphology. In this study, we found that mtKRAS specifically induced the dysregulated expressions of phosphodiesterase 4B (PDE4B), Alpha Kinase 2, miR-181, miR-210 and genes associated with the stroma ingredient etc. in 3D culture but not in 2D culture. Furthermore, we found that PDE4 inhibitors, including rolipram and resveratrol, induced luminal apoptosis in HCT116 spheroids. These results suggest that mtKRAS-mediated signaling in 3D environment is a target for cancer therapy and is also associated with cancer-stroma interaction (field effect).
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Zfat-deficiency results in a loss of CD3zeta phosphorylation with dysregulation of ERK and Egr activities leading to impaired positive selection.2013
Author(s)
Ogawa M, Okamura T, Ishikura S, Doi K, Matsuzaki H, Tanaka Y, Ota T, Hayakawa K, Suzuki H, Tsunoda T, Sasazuki T and Shirasawa S
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] KRAS up-regulates the expression of miR-181a, miR-200c and miR-210 in a three-dimensional-specific manner in DLD-1 colorectal cancer cells.2012
Author(s)
Ota T, Doi K, Fujimoto T, Tanaka Y, Ogawa M, Matsuzaki H, Kuroki M, Miyamoto S, Shirasawa S, Tsunoda T.
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Journal Title
Anticancer Res.
Volume: 32
Pages: 2271-5
Related Report
Peer Reviewed
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[Journal Article] ALPK2 is crucial for luminal apoptosis and DNA repair-related gene expression in a three-dimensional colonic-crypt model.2012
Author(s)
Yoshida Y, Tsunoda T, Doi K, Fujimoto T, Tanaka Y, Ota T, Ogawa M, Matsuzaki H, Kuroki M, Iwasaki A, Shirasawa S.
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Journal Title
Anticancer Res.
Volume: 32
Pages: 2301-8
Related Report
Peer Reviewed
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