2020年10月23日
The Loss of Nuclear PTEN Increases Tumorigenesis in a Preclinical Mouse Model for Hepatocellular Carcinoma.
iScience
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- 巻
- 23
- 号
- 10
- 開始ページ
- 101548
- 終了ページ
- 101548
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.isci.2020.101548
The PTEN gene is highly mutated in many cancers, including hepatocellular carcinoma. The PTEN protein is located at different subcellular regions-PTEN at the plasma membrane suppresses PI3-kinase signaling in cell growth, whereas PTEN in the nucleus maintains genome integrity. Here, using nuclear PTEN-deficient mice, we analyzed the role of PTEN in the nucleus in hepatocellular carcinoma that is induced by carcinogen and oxidative stress-producing hepatotoxin. Upon oxidative stress, PTEN was accumulated in the nucleus of the liver, and this accumulation promoted repair of DNA damage in wild-type mice. In contrast, nuclear PTEN-deficient mice had increased DNA damage and accelerated hepatocellular carcinoma formation. Both basal and oxidative stress-induced localization of PTEN in the nucleus require ubiquitination of lysine 13 in PTEN. Taken together, these data suggest the critical role of nuclear PTEN in the protection from DNA damage and tumorigenesis in vivo.
- リンク情報
- ID情報
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- DOI : 10.1016/j.isci.2020.101548
- PubMed ID : 33083717
- PubMed Central 記事ID : PMC7516300