| Project/Area Number |
17K08698
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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 | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
村田 雅樹 札幌医科大学, 医学部, 講師 (10404592)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 子宮頸部腺がん / エストロゲン受容体 / GPR30 / 病理学 / 子宮頸部 / 子宮頸部腺癌 / エストロゲン / 子宮頚部 |
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| Outline of Final Research Achievements |
The expression of GPR30 was analyzed in the surgical specimen of uterine cervical adenocarcinoma. GPR30 was significantly high expressed in adenocarcinoma than in non-tumor glandular epithelium. Patients with each higher GPR30 and claudin-1 expression had a worse prognosis. GPR30 and ER expression were negatively correlated, suggesting that ER may function as an estrogen receptor in normal glandular epithelium and GPR30 in adenocarcinoma tissue. We identified several proteins that increase with GPR30 agonist exposure to several cell lines. When protein X was deleted by the CRISPR-Cas9 system, proliferation ability and the like were remarkably suppressed. It was suggested that GPR30 may be involved in malignant transformation of cervical adenocarcinoma via multiple proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮頸部腺がんは、予後が悪く、患者数が増加しているものの、その自然史は十分に理解されていない。本研究では、頸部腺がんの悪性化に関与する機序の一部が明らかになった。特に、古典的エストロゲン受容体が発現していないことから、エストロゲン非依存性癌と理解されてきた頸部腺がんに、膜型エストロゲン受容体GPR30が発現し、claudin-1を介して悪性化に関与していることを明らかにした。この結果は、頸部腺がんがエストロゲン依存性癌である可能性を示すものであり、頸部腺がん患者の治療戦略を変える可能性がある。
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