The elucidation of molecular mechanism of maspin related with unfavorable prognosis of human breast cancer patients
| Project/Area Number |
16K10458
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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 |
General surgery
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
坂部 友彦 鳥取大学, 医学部, 助教 (50639747)
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| Research Collaborator |
WAKAHARA makoto
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 乳癌 / Maspin / 予後 / 上皮間葉転換 / 細胞内局在 / 浸潤 / EMT / 細胞浸潤 / 細胞増殖 / アンプリコンシークエンス / maspin |
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| Outline of Final Research Achievements |
Maspin is known to be a tumor suppressor gene. However, we revealed that cytoplasmic maspin (cytMaspin) expression was an indicator of poor prognosis in human breast cancer patients. Therefore, we investigate the function of cytMaspin in human breast cancer cells. Expression of maspin in MDA-MB-231 mainly exhibited a cytoplasmic localization, whereas that in MCF10A (normal mammary epithelial cells) exhibited nuclear and cytoplasmic localization. Maspin overexpression promoted cell invasion in MDA-MB-231, while downregulation of maspin induced the opposite effect.
To investigate how cytoplasmic maspin regulates cancer cell invasion, we focused on the EMT. In MDA-MB-231 overexpressing maspin, E-cadherin expression was decreased, while N-cadherin expression was increased. Furthermore, Maspin overexpression increased EMT-related transcription factors (Slug, Twist, ZEB1 and ZEBs2). CytMaspin may contributes to the regulation of cancer cell invasion via a process related with EMT.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、癌抑制遺伝子とされているMaspinが、ある種の乳癌培養細胞株において細胞質に発現しており、増殖能および浸潤能の亢進によって癌の進展に関与していることが示唆された。これらは、免疫組織化学を用いた我々の研究結果を支持するものであった。また、細胞質局在型Maspinの発現は、複数の上皮間葉転換関連遺伝子の発現と正の相関を示すことを見い出した。これらの結果より、乳癌における新たな治療標的分子同定の基礎研究発展に繋がることが期待できる。また、Maspinは乳癌のみならず様々な癌腫に発現していることから、他の癌腫に対しても応用可能な基盤研究となることが期待される。
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Report
(4 results)
Research Products
(6 results)
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[Presentation] Clinical Significance of Subcellular Localization of Maspin in Patients with Pathological Stage IALung Adenocarcinoma2018
Author(s)
Ohno.T, Nozaka.Y, Fujiwara.W, Miyamoto.T, Kadonaga.T, Kidokoro.Y, Wakahara.M、Takagi.Y, Tanaka.Y, Haruki.T, Miwa.K, Suzuki.Y, Taniguchi.Y, Nakamura.H and Umekita.Y
Organizer
IASLC 19th World Conference on Lung Cancer
Related Report
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