2022 Fiscal Year Final Research Report
Chromosomal instability and its relation to the mechanism underlying multiple development of cancer
| Project/Area Number |
20K08940
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
Noda Hiroshi 自治医科大学, 医学部, 教授 (00382937)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
鈴木 浩一 自治医科大学, 医学部, 教授 (70332369)
力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Keywords | 多発癌 / 染色体不安定性 / セントロメア / Satellite α transcript / 脱メチル化異常 |
|---|
| Outline of Final Research Achievements |
We constructed a lentiviral vector containing Majar SatA (mSatA) sequence of the mouse and used it in a mouse model of mammary carcinogenesis. When DMBA (7,12-Dimethylbenz(a)anthracene)
was administered orally and lentivirus was administered into the mammary ducts of mice to promote mammary cancer development, it was not observed macroscopically in either the intervention group or the control group within the observation period. Therefore, we discontinued to use a lentiviral vector carrying the mouse mSatA sequence and created a retroviral vector. A retroviral vector led to overexpression of mSAT, which increased the percentage of cells with mitotic defects such as abnormal segregation, micronuclei and anaphase bridges compared to controls. We are preparing to administer this vector to mice and evaluate how long and how many breast cancer occurs, the frequency of multiple and multi-organ development, changes in copy number of chromosome, and gene expression.
|
| Free Research Field |
腫瘍外科
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、多発癌発生のメカニズムを、脱メチル化異常を背景としたSatAが誘導する「field cancerization」と関連づけて検証する独創的な研究課題です。昨今の縮小手術の普及は異時性発癌のリスクをさらに助長すると懸念されます。「field cancerization」という腫瘍学的な視点から、術式の選択を再考する重要な転機になると考えられます。多発癌発生の頻度や時期、さらに他の異時発癌の標的臓器を明らかにする事ができれば、スクリーニングの時期や対象臓器を含めた検査方法の決定など、臨床応用への貢献が期待されます。
|
