| Project/Area Number |
17K16607
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory surgery
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| Research Institution | Osaka University |
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Principal Investigator |
Kimura Kenji 大阪大学, 医学部附属病院, 医員 (50795325)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肺癌 / 発癌 / 肺異型腺腫様過形成 / 肺腺癌 / 異型腺腫様過形成 |
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| Outline of Final Research Achievements |
Atypical adenomatous hyperplasia (AAH) is classified as a precancerous lesion and is thought to progress to an invasive cancer. We focused on Arl4c, which is downstream of EGF / Ras and Wnt signals and has been reported to be involved in the growth and migration ability of lung cancer. Mutated KRAS (KrasG12V) and/or Arl4c were introduced into the normal human small airway epithelial cell (SAEC). Cell proliferation of SAEC expressing KrasG12V and Arl4c was remarkably higher than that of SAEC expressing control. Phosphorylation of ERK1/2 was also upregulated in SAEC/KrasG12V/Arl4c. Furthermore, using the specimens resected from patients, Arl4c expression was immunohistochemically examined in AAH. The positive rate of Arl4c was high (79%). From the above, in addition to mutated KRAS, Arl4c also may be involved in the pathogenesis of AAH, which is a process of lung adenocarcinoma development.
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| Academic Significance and Societal Importance of the Research Achievements |
肺腺癌の前癌病変(AAH)で特異的に発現し、癌化の過程に直接的に関わる遺伝子変異は明らかにされていない。AAH発生の機序を解明して、肺腺癌発症の機序を明確化することは今後の治療薬開発などにおいても重要である。申請者は、肺腺癌の癌化に関わる遺伝子変異を明らかにし、新たな肺癌治療を考案することを目的に研究を開始した。今回、AAHの病態を反映した細胞実験と臨床検体を用いた実験の両面からAAHの病態にArl4c分子が関与している可能性を示したのは初めてのことである。このことは、新たな肺癌治療を考案するのみならず肺癌予防医学にも多大な貢献が期待できると考えられる。
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