The analysis of the p53 isoforms in hepatocellular carcinoma cells using endogenous gene modification.
| Project/Area Number |
16K09381
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Aichi Medical University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
太田 明伸 愛知医科大学, 医学部, 講師 (30438048)
稲熊 真悟 愛知医科大学, 医学部, 講師 (80410786)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | p53 / isoform / CRSPR/CAS9 / 肝癌 / p53α / p53β / 細胞周期 / アポトーシス / p53 isoform / 肝細胞癌 / delta40p53 / delta133p53 / p53beta / cellular senescence / tumor suppression / p53アイソフォーム / TP53遺伝子 / CRSPR/Cas9 / 内在性遺伝子改変 / 細胞老化 / 細胞増殖能 / CRISPR/Cas9 / 遺伝子ターゲッティング法 |
|---|
| Outline of Final Research Achievements |
We established several hepatocellular carcinoma cell lines of which endogenous TP53 alleles were modified using CRSPR/CAS9 system, and analyzed the function of several p53 splicing isoforms. We reported that △40p53α suppressed tumor cell proliferation and induced cellular senescence in hepatocellular carcinoma cells (J cell Sci 2017; 130(3): 614-625). △133p53α and △133p53β, which have same structure in C-terminal but different in N-terminal, also showed the function as same as △40p53α. However, △133p53αwas combined with △133p53α, but △133p53βwas not. The cDNA array analysis suggested that target gene expression pattern to each isoform was different. In the animal experiment of p53 isoforms, the expression of full-length p53 decreased with aging in control rats, but did not in diabetes model rats. We are analyzing the detail more.
|
| Academic Significance and Societal Importance of the Research Achievements |
肝癌は本邦で年間3万人以上が死亡しており、肝癌の制御と撲滅は急務であるが癌の分子機構は不明な点が多い。発癌には複数の癌抑制遺伝子が関与するが、その中でもp53は多くの癌種に関与する重要な蛋白質である。近年、蛋白質のアイソフォームの重要性が認識され、その解析に注目が集まっている。我々は発癌に重要なp53蛋白質アイソフォームの肝癌における機能に着目して研究し、その一つである△40p53の肝癌での機能を世界で初めて報告した。p53には10以上のアイソフォームがあり他のp53アイソフォームにも研究を発展させた。p53アイソフォームの機能を解析することは発癌のおける分子機構の解明に貢献すると思われる。
|
Report
(4 results)
Research Products
(6 results)
-
[Journal Article] Delta40p53 suppresses tumor cell proliferation and induces cellular senescence in hepatocellular carcinoma cells2017
Author(s)
Ota A, Nakao H, Sawada Y, Karnan S, Wahiduzzaman M, Inoue T, Kobayashi Y, Yamamoto T, Ishii N, Ohashi T, Nakade Y, Sato K, Itoh K, Konishi H, Hosokawa Y, Yoneda M
-
Journal Title
J Cell Sci
Volume: 130
Issue: 3
Pages: 614-625
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Presentation] Delta40p53 suppresses tumor cell proliferation and induces cellular senescence in hepatocellular carcinoma cells.2018
Author(s)
Haruhisa Nakao, Akinobu Ota, Yumi Sawada, Sivasundaram Karnan, Md Wahiduzzaman, Tadashi Inoue, Yuji Kobayashi,Norimitsu Ishii, Tomohiko Ohashi, Yukiomi Nakade, Yoshio Sumida, Kiyoaki Itoh, Hiroyuki Konishi, Yoshitaka Hosokawa, Masashi Yoneda
Organizer
the European Association for the Study of Liver: The International Liver Congress 2018 in Paris
Related Report
Int'l Joint Research
-
[Presentation] Delta133p53, One of the p53 Isoforms, Suppresses Tumor Cell Proliferation and Induces Cellular Senescence in Hepatocellular Carcinoma Cells2018
Author(s)
Haruhisa Nakao, Akinobu Ota, Mayu Ibusuki, Rena Kitano, Satoshi Kimoto, Tomohiko Ohashi, Yukiomi Nakade, Yoshio Sumida, Kiyoaki Itoh, Hiroyuki Konishi, Yoshitaka Hosokawa, Masashi Yoneda
Organizer
the American Association for the Study of Liver Diseases. : The Liver Meeting® 2018 in San Francisco
Related Report
Int'l Joint Research
-
-
