Normal and tumor suppressive function of p53 family genes and their therapeutic application
Project/Area Number |
17K07152
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | Tohoku University |
Principal Investigator |
Ikawa Shuntaro 東北大学, 加齢医学研究所, 准教授 (50241576)
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Project Period (FY) |
2017-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | p53ファミリー遺伝子 / 乳癌 / 始源生殖細胞 / 幹細胞 / 分化 / アポトーシス / 2)始源生殖細胞 / 乳がん / p63 / 放射線 / エストロゲン受容体 / がん抑制遺伝子 / miRNA / p53ファミリー / 生殖細胞 / 発生 |
Outline of Final Research Achievements |
ΔNp63α (p53 family genes)expression in MCF7, estrogen receptor positive (ER+) luminal breast cancer cells, led to quiescence and acquisition of progenitor cell-like properties. We found that this phenomenon is caused by ΔNp63α dependent induction of miR-205 leading to downregulation of BRCA1 pathway. Furthermore, we found that p63α/β expression is associated with better relapse- and metastasis-free survival of ER+ and/or luminal A-type patients, but not of the other subtypes. We also found that primordial germ cells are much more sensitive to radiation and anti-tumor drugs compared to somatic cells. This phenomenon turned out to be caused by overall reduction of anti-apoptotic miRNA contrasting to the induction of pro-apoptotic genes, which is commonly involved in ordinary apoptotic programs.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で見出したluminalA/Bタイプの乳がんにおいてp63の発現量が高いと予後が良いことを見出した。このことからΔNp63α発現が、luminal typeの乳がんにおいて、quiescenceを誘導し、がん細胞を潜在的な状態に保持することが、乳がんの長期にわたるdormancyのメカニズムの一つであることが示唆された。一見治癒したように見えても、5年以上経過してから再発転移することが知られている乳がんの治療法の改善にも寄与しうる。始源生殖細胞の研究は、放射線被ばくを受けたり、放射線治療を受ける女性、男性の生殖細胞の保持に指針を与えることが期待され、研究を進める。
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Report
(7 results)
Research Products
(6 results)
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[Journal Article] Intracellular S1P Levels Dictate Fate of Different Regions of the Hippocampus following Transient Global Cerebral Ischemia.2018
Author(s)
Rashad S, Niizuma K, Saigusa D, Han X, Sato-Maeda M, Saito R, Uruno A, Fujimura M, Ikawa S, Yamamoto M, Tominaga T.
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Journal Title
Neuroscience
Volume: 384
Pages: 188-202
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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