2022 Fiscal Year Final Research Report
The functional role of chromatin regulator in established PDAC
| Project/Area Number |
19H03639
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
妹尾 浩 京都大学, 医学研究科, 教授 (90335266)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 膵癌 / 分子機序 / クロマチンリモデリング因子 |
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| Outline of Final Research Achievements |
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses among all human malignancies. It is urgently needed to develop novel therapeutic approaches for this lethal disease. We previously reported that BRG1/SOX9 axis is required for PDAC formation in mice and that BRG1 is expressed in approximately 80 % of human PDAC. In this study, we aimed to clarify the functional role of Brg1 in established PDAC in mice using a dual recombinase system and in human PDAC cells. We found that ①Brg1 knockout (KO) in established PDAC leads to increased apoptosis and reduced growth in mice. ②BRG1 is required for metastasis of PDAC cells in mice. ③Brg1 plays a critical role for cancer stemness of PDAC cells. ③ BRG1 knockdown (KD) or KO leads to increased apoptosis and decreased cell growth in human PDAC cells in vitro and in vivo. These data indicate that Brg1 could be a novel therapeutic target for PDAC.
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| Free Research Field |
消化器内科
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| Academic Significance and Societal Importance of the Research Achievements |
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses among all human malignancies. It is urgently needed to develop novel therapeutic approaches for this lethal disease. This study revealed that Brg1 is required for established PDAC and could be a novel therapeutic target for PDAC.
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