Project/Area Number |
24591985
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Toho University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
KOIKE Junichi 東邦大学, 医学部, 講師 (30339155)
ARITA Michitsune 東邦大学, 医学部, 助教 (80307719)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | ゲノム不安定性 / EMAST / 大腸がん / p53 / 低酸素 / DNAミスマッチ修復 / DNAミスマッチ修復遺伝子 / DNAミスマッチ遺伝子 |
Outline of Final Research Achievements |
Microsatellite instability (MSI) is a hypermutable phenotype in human cancers. Elevated microsatellite alterations at select tetranucleotides (EMAST), distinct from MSI-high and MSI-low, found in around 60% of colorectal cancer in Japan and USA. Here, we studied molecular events accompanying with generation of EMAST. First, we succeeded establishment of in vitro system for EMAST generation using human colorectal cell lines. p53 gene mutation and long-term cultivation under hypoxia is important for the generation. Pathways and changes in gene expression were mostly known as Warburg effects. However, characteristic molecules such as caveolins and keratin-associated proteins were found. In addition, inhibitors of such pathways and molecules were listed. Whether these inhibitors and characteristic molecules are really useful for cure and/or diagnosis for colorectal cancer, further detailed studies are required.
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