| Project/Area Number |
17K09364
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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 |
Gastroenterology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
塩谷 昭子 川崎医科大学, 医学部, 教授 (80275354)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | バレット食道腺癌 / PDZK1 / バレット腺癌 / LSBE / SSBE / SERPINB7 |
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| Outline of Final Research Achievements |
In a previous study, we found that PDZK1 expression is higher in long segment BE compared to that in short-segment BE. Human adenocarcinoma-derived OE33 cells were used as a parental cell line and transfected to generate PDZK1 overexpressed OE33 cells (PC cells) or transfected with empty vector as control cells (NC cells).
There were no significant differences in cell growth between NC and PC cells. PSI significantly increased apoptosis in NC cells, but not in PC cells. In response to PSI, increased levels of cleaved-caspase3 and decreased pro-caspase3 levels were found in NC cells, but not in PC cells. In NC cells, PSI significantly decreased Bcl-2 expression without affecting Bax levels. In contrast, high expression of both Bcl-2 and Bax was observed in PC cells.
Overexpression of PDZK1 protein induces an apoptosis-resistant phenotype in BE cells, which may be a potential therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、下部食道のバレット上皮から発生する食道腺癌は急激な増加を示し、海外において最も増加率が高い癌である。
我々は米国人と日本人の検体を用いて癌の合併率が高いバレット上皮においてPDZK1の発現が高いことを調べてきた。今回、PDZK1の役割を明らかにする目的で食道腺癌細胞株にPDZK1を過剰発現させた細胞を作成した。対照の細胞と比較すると細胞の増殖速度に差は認めなかったが、アポトーシス（細胞が構成している組織をより良い状態に保つため、細胞自体に組み込まれた細胞の自然死）刺激を行うと、アポトーシスの増加抑制を認めた。そのためPDZK1は食道腺癌において癌の抵抗性を増加させる可能性が考えられた。
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