New mechanism of teratoma formation associated with GANP function.
| Project/Area Number |
20K16228
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49030:Experimental pathology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 奇形腫マウスモデル / GANP / 始原生殖細胞 / 奇形腫発生 / 精巣奇形腫 / 転写共役型DNA傷害 / 奇形腫 / 精巣 / R-loop |
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| Outline of Research at the Start |
奇形腫はヒト iPS 細胞や ES 細胞の移植の際に発生する腫瘍で，再生医療の進歩の足枷になっている．申請者等は GANP タンパクを過剰発現させたトランスジェニックマウスを作製したところ，高確率に精巣・子宮に奇形腫が自然発生することを発見した．本研究は，①奇形腫等の腫瘍における GANP の発現解析，②GANP を介した DNA 傷害と奇形腫発生の関係解明，③幹細胞性に着目した奇形腫細胞における GANP の機能解析，を目的とする．モデルマウス・分子生物学的解析のみならず，ヒト組織検体を用いた解析まで交えて複合的に行い，ヒト奇形腫の発症メカニズムを GANP の機能面から明らかにする．
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| Outline of Final Research Achievements |
We analyzed the expression of GANP in human testicular postpubertal-type teratomas and established a novel mouse model to reveal the association between GANP and teratomagenesis.
We analyzed 31 cases of human testicular postpubertal-type teratomas and, in all cases, GANP was overexpressed. The aberrant expression was also detected in germ cell neoplasia in situ (GCNIS) accompanied by the teratoma. To further clarify the association between GANP and teratomagenesis, we established a novel teratomagenesis mouse model (CAG-ganp Tg mice). In the GANP－teratoma mice, GANP-overexpressing teratomas were more frequent at the testes and the middle portion of the uterus than has been seen in the previously established mouse models.
In conclusion, GANP is overexpressed in testicular postpubertal-type teratomas and is an essential teratomagenic factor.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトiPS細胞を用いた再生医療は疾患の治療に飛躍的な進歩をもたらす可能性を秘めているが、現在では移植による奇形腫の発生が大きな問題となっている。このことを克服するために奇形腫発生制御の研究が世界中で進められている。しかし、従前より使用されている奇形腫好発系のマウス129/Sv系統や129+Ter/Sv系統でも奇形腫の発生率は極めて低く。奇形腫の分子生物学的解析は困難を極めていた．私たちは奇形腫発生のメカニズムにGANPが密接に関係していることを明らかにしたと同時に、CAG-ganp Tgマウスは奇形腫発生率が高く、奇形腫発生を制御するための新しい技術開発にも極めて有用であることが分かった。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Testicular teratomagenesis from primordial germ cells with overexpression of germinal center-associated nuclear protein2023
Author(s)
Yasuhiro Sakai, Kazuya Yoshinaga, Ayaka Yoshida, Andri Rezano, Kazuya Shiogama, Yoshiaki Kawashima, Tadashi Yoshizawa, Akihiko Yoshizawa, Shingo Hatakeyama, Chikara Ohyama, Hiroyasu Ito, Masato Abe, Hiroshi Kijima, Yoshiro Otsuki, Akihiko Ito, Toyonori Tsuzuki, Motohiro Takeya, Nobuo Sakaguchi & Kazuhiko Kuwahara
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Journal Title
Cancer Science
Volume: 114
Issue: 4
Pages: 1729-1739
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Cytomorphology and Gene Expression Signatures of Anchorage-independent Aggregations of Oral Cancer Cells2023
Author(s)
Kouhei Sakurai, Akira Nagai, Tatsuya Ando, Yasuhiro Sakai, Yuka Ideta, Yuichiro Hayashi, Junichi Baba, Kenji Mitsudo, Masaharu Akita, Nobutake Yamamichi, Hidetsugu Fujigaki, Taku Kato, Hiroyasu Ito
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Journal Title
Cancer Genomics Proteomics
Volume: 20
Issue: 1
Pages: 64-74
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transcriptome of sessile serrated adenoma/polyps is associated with MSI-high colorectal cancer and decreased expression of CDX22022
Author(s)
Daisuke Ohki, Nobutake Yamamichi, Yoshiki Sakaguchi, Yu Takahashi, Natsuko Kageyama-Yahara, Mitsue Yamamichi, Chihiro Takeuchi, Yosuke Tsuji, Yasuhiro Sakai, Kouhei Sakurai, Shuta Tomida, Kazuhiko Koike, Mitsuhiro Fujishiro
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Journal Title
Cancer Medicine
Volume: 00
Issue: 24
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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