https://scholars.lib.ntu.edu.tw/handle/123456789/473391
標題: | Depletion of β-catenin from mature hepatocytes of mice promotes expansion of hepatic progenitor cells and tumor development | 作者: | Wang E.-Y. Shiou-Hwei Yeh Tsai T.-F. HSIANG-PO HUANG YUNG-MING JENG Lin W.-H. Chen W.-C. KUN-HUEI YEH PEI-JER CHEN Chen D.-S. |
公開日期: | 2011 | 出版社: | National Academy of Sciences | 卷: | 108 | 期: | 45 | 起(迄)頁: | 18384-18389 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | Depletion of β-catenin impairs regeneration of the rapid turn-over gut epithelial cells, but appears dispensable for that of the slow turn-over mature hepatocytes in mice until 1 y of age. As the life span of mature murine hepatocytes is about 400 d, we studied conditional β-catenin knockout mice (Alb-Cre;Ctnnb1flx/flx) until 20 mo of age to determine the function of β-catenin in the postnatal liver. β-catenin was absent from the hepatocytes of β-catenin knockout mice 4 wk after delivery. From 9 mo of age, hepatocytes were gradually replaced by newly formed β-catenin-positive hepatocytes, which constituted about 90% of hepatocytes at 18-20 mo of age. This process was accompanied by active proliferation of bile duct/ductule cells. β-catenin-positive hepatocytes exhibited elevated proliferation activity and expression of progenitor cell markers, but lower albumin and Cre. This might explain their intact β-catenin protein, and suggest their origins from hepatic progenitor cells. Liver tumors arose spontaneously from β-catenin-positive cells, and tumorigenesis was accelerated by hepatitis B X protein. These results indicate β-catenin critical for the regeneration of mature hepatocytes. Failure to regenerate mature hepatocytes results in proliferation of hepatic progenitor cells that are able to maintain liver function but are predisposed to form liver tumors. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983727002&doi=10.1073%2fpnas.1116386108&partnerID=40&md5=38a6ad3ee0de914d2431d5c50d90d1f1 https://scholars.lib.ntu.edu.tw/handle/123456789/473391 |
ISSN: | 0027-8424 | DOI: | 10.1073/pnas.1116386108 | SDG/關鍵字: | albumin; beta catenin; cell marker; creatine; hepatitis B virus X protein; age; albumin blood level; animal cell; article; bile duct; carcinogenesis; cell maturation; cell proliferation; cell regeneration; creatine kinase blood level; knockout mouse; liver cell; liver function; liver tumor; mouse; nonhuman; perinatal period; priority journal; protein depletion; protein function; stem cell; tumor growth; Murinae; Mus |
顯示於: | 病理學科所 |
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