| Project/Area Number |
19K22595
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 52:General internal medicine and related fields
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
Harada Hiroshi 京都大学, 生命科学研究科, 教授 (80362531)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
森鳰 章代 京都大学, 生命科学研究科, 研究員 (20722648)
小林 稔 京都大学, 生命科学研究科, 特定助教 (40644894)
|
|---|
| Project Period (FY) |
2019-06-28 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
|
|---|
| Keywords | がん / 低酸素 / 浸潤・転移関連遺伝子 / 放射線治療 / 放射線抵抗性 / HIF-1 / 再発 / 浸潤 / 抵抗性 |
|---|
| Outline of Research at the Start |
がん細胞が酸素・栄養環境の悪い領域から良い領域へと浸潤する際に必要な責任遺伝子を網羅的に探索し、同定した遺伝子が放射線治療後の再発で果たす機能を解明する。そして、同定した遺伝子の作用機序を解明し、その働きを阻害する手法の確立に繋げる。再発を担う責任因子の同定という探索研究を基に、放射線治療効果の増強に繋がる新規治療コンセプトを確立を目指す。
|
| Outline of Final Research Achievements |
We previously demonstrated in cell lineage experiments of hypoxic cancer cells that cancer cells responsible for tumor recurrence after radiation therapy are predominantly present in hypoxic regions within a tumor tissue. It was also clarified that during the recurrence process, hypoxic cancer cells that survive radiation therapy infiltrate toward the tumor blood vessels, causing cancer recurrence. However, the gene that induces the infiltration ability of hypoxic cancer cells has not been identified yet. In this study, we developed a screening experiment to search for the gene and could successfully identify a novel gene. We found that the expression of the gene was induced at the transcription initiation level in a hypoxia-inducible transcription factor (HIF-1)-dependent manner. An in vitro scratch assay also confirmed its ability to induce invasiveness of cancer cells under hypoxia.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、低酸素がん細胞の浸潤能を担う新たな責任遺伝子を同定することが出来、かつその発現制御機構の一端が明らかになった。今後、更に発現制御機構の詳細を明らかにすることで、当該新規遺伝子の機能を阻害し、がんの浸潤能を抑制、そして放射線治療後の再発を抑える新たな治療法の確立に繋がることが期待される。
|
