2022 Fiscal Year Final Research Report
Exploring Liver Cancer-Specific Wnt Signaling Abnormalities by High-precision Analysis of TCF-4 Isoform Expressions
| Project/Area Number |
20K08345
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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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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | T-cell factor-4 / Wnt / Isoform / Splice variant |
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| Outline of Final Research Achievements |
Previous studies have suggested that the expression levels and ratios of each TCF-4 isoform regulate the variety of hepatocellular carcinoma traits, but our previous analysis methods are limited in their quantitativeness. In this study, we have overcome this limitation with a new PCR system using peptide nucleic acids. Comparison of TCF-4J with TCF-4K expression showed that TCF-4J type is strongly expressed in gastrointestinal cancers such as stomach and colon, rather than the liver. We also found that TCF-4E is specifically highly expressed in fetus-derived immortalized hepatocytes. The results suggest that TCF-4 isoform profiles reflect cancer aggressiveness and organ-specific Wnt signaling activation status.
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| Free Research Field |
消化器病学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，14種すべてのTCF-4 isoformを解析対象とした．その結果，TCF-4M以外の13種のisoforｍの半定量的測定が可能であった．この測定系を初めて開発したことで，今後も独自に種々の腫瘍細胞や組織におけるTCF-4 isoformのプロファイル解析が可能となった．また，癌微小環境において，TCF-4 isoformプロファイルとWntシグナル活性との相関を評価することが可能となり，Wntシグナルを標的とする創薬研究にも大きく貢献できると考えている．
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