The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas
Open accessAbstract
PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePten(flox/flox) mice). AlbCrePten(flox/flox) mice showed massive hepatomegaly and steatohepatitis with triglyceride accumulation, a phenotype similar to human nonalcoholic steatohepatitis. Adipocyte-specific genes were induced in mutant hepatocytes, implying adipogenic-like transformation of these cells. Genes involved in lipogenesis and beta-oxidation were also induced, possibly as a result of elevated levels of the transactivating factors PPARgamma and SREBP1c. Importantly, the loss of Pten function in the liver led to tumorigenesis, with 47% of AlbCrePten(flox/flox) livers developing liver cell adenomas by 44 weeks of age. By 74-78 weeks of age, 100% of AlbCrePten(flox/flox) livers showed adenomas and 66% had hepatocellular carcinomas. AlbCrePten(flox/flox) mice also showed insulin hypersensitivity. In vitro, AlbCrePten(flox/flox) hepatocytes were hyperproliferative and showed increased hyperoxidation with abnormal activation of protein kinase B and MAPK. Pten is thus an important regulator of lipogenesis, glucose metabolism, hepatocyte homeostasis, and tumorigenesis in the liver.
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Metadata
- Authors
- Horie, Y., Suzuki, A., Kataoka, E., Sasaki, T., Hamada, K., Sasaki, J., Mizuno, K., Hasegawa, G., Kishimoto, H., Iizuka, M., Naito, M., Enomoto, K., Watanabe, S., Mak, T. W., & Nakano, T.
- Venue
- Journal of Clinical Investigation
- Published
- 2004-06-15
- Volume
- 113
- Issue
- 12
- Pages
- 1774-1783
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2141956267
- Cited by
- 698
- References
- 62
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Horie, Y., Suzuki, A., Kataoka, E., Sasaki, T., Hamada, K., Sasaki, J., Mizuno, K., Hasegawa, G., Kishimoto, H., Iizuka, M., Naito, M., Enomoto, K., Watanabe, S., Mak, T. W., & Nakano, T. (2004). Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. Journal of Clinical Investigation. https://doi.org/10.1172/jci200420513
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