2019 Fiscal Year Final Research Report
The functional analyses and the therapeutic applications of a novel tumor suppressor gene ZNF395 involved in the progression of pancreatic cancers.
| Project/Area Number |
17K08695
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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 |
Human pathology
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
兒玉 雅明 大分大学, 福祉健康科学部, 教授 (20332893)
泥谷 直樹 大分大学, 医学部, 准教授 (80305036)
守山 正胤 大分大学, 医学部, 教授 (90239707)
沖本 忠義 大分大学, 医学部, 講師 (90381037)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 膵癌 / ZNF395 / がん抑制遺伝子 / 細胞周期 |
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| Outline of Final Research Achievements |
To elucidate the functional significance of downregulation of ZNF395 due to 8p loss in pancreatic carcinogenesis, pancreatic cancer cell lines for doxycycline-inducible expression of ZNF395 were established. The proliferation potentials were markedly suppressed through a cell cycle arrest by induction of ZNF395. Immunohistochemical analyses of resected pancreatic cancer tissues revealed that the expression of ZNF395 was observed in cytoplasm of non-tumorous pancreatic ducts and acinar glands. In addition, it was detectable in intraepithelial lesions. On the other hand, ZNF395 expression was significantly reduced in the cancer cells in invasive lesions, especially in these with poor differentiation. Downregulation of ZNF395 showed a tendency to be worse prognosis in the patients with pancreatic cancers.
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| Free Research Field |
人体病理学
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| Academic Significance and Societal Importance of the Research Achievements |
膵前癌病変が浸潤癌へ進展する分子メカニズムの一部を明らかにした。8p欠失に伴うZNF395の発現低下は膵癌前駆細胞に細胞周期の脱制御と増殖能亢進をもたらした。今後、ZNF395の下流で活性化されるシグナルパスウェイの同定を目指す。本研究で得られる知見は、新規の膵癌早期診断法および分子標的治療法の開発に応用可能である。予後不良な難治癌である膵癌の治療成績の向上に寄与することを期待する
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