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Your search keyword '"Suzuki, Akira"' showing total 2 results
2 results on '"Suzuki, Akira"'

1. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas.

Author

Horie, Yasuo, Suzuki, Akira, Kataoka, Ei, Sasaki, Takehiko, Hamada, Koichi, Sasaki, Junko, Mizuno, Katsunori, Hasegawa, Go, Kishimoto, Hiroyuki, Iizuka, Masahiro, Naito, Makoto, Enomoto, Katsuhiko, Watanabe, Sumio, Mak, Tak Wah, and Nakano, Toru

Subjects
*LIVER physiology, *PROTEIN metabolism, *ANIMAL experimentation, *ANTHROPOMETRY, *CELLULAR signal transduction, *COMPARATIVE studies, *EPITHELIAL cells, *ESTERASES, *FAT cells, *GENES, *GENETIC disorders, *GENETIC techniques, *HEPATITIS, *HEPATOCELLULAR carcinoma, *HOMEOSTASIS, *INSULIN, *LIPIDS, *LIPID metabolism disorders, *LIVER, *LIVER tumors, *RESEARCH methodology, *MEDICAL cooperation, *MICE, *PHOSPHATASES, *PHOSPHORYLATION, *PROTEINS, *RESEARCH, *PHENOTYPES, *EVALUATION research, *CELL physiology
Abstract

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. [ABSTRACT FROM AUTHOR]

Published
2004
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2. Pten controls lung morphogenesis, bronchioalveolar stem cells, and onset of lung adenocarcinomas in mice.

Author

Yanagi, Shigehisa, Kishimoto, Hiroyuki, Kawahara, Kohichi, Sasaki, Takehiko, Sasaki, Masato, Nishio, Miki, Yajima, Nobuyuki, Hamada, Koichi, Horie, Yasuo, Kubo, Hiroshi, Whitsett, Jeffrey A., Tak Wah Mak, Nakano, Toru, Nakazato, Masamitsu, Suzuki, Akira, and Mak, Tak Wah

Subjects
*ADENOCARCINOMA, *CARDIOPULMONARY system, *RESPIRATORY organs, *CELLULAR pathology, *PHYSIOLOGICAL control systems, *GENETIC toxicology, *LUNG abnormalities, *ANIMAL experimentation, *BRONCHI, *GENE expression, *LUNGS, *LUNG tumors, *MICE, *MORPHOGENESIS, *GENETIC mutation, *PHOSPHATASES, *PULMONARY alveoli, *RESPIRATORY mucosa, *STEM cells, *NEOPLASTIC cell transformation
Abstract

PTEN is a tumor suppressor gene mutated in many human cancers. We generated a bronchioalveolar epithelium-specific null mutation of Pten in mice [SP-C-rtTA/(tetO)(7)-Cre/Pten(flox/flox) (SOPten(flox/flox)) mice] that was under the control of doxycycline. Ninety percent of SOPten(flox/flox) mice that received doxycycline in utero [SOPten(flox/flox)(E10-16) mice] died of hypoxia soon after birth. Surviving SOPten(flox/flox)(E10-16) mice and mice that received doxycycline postnatally [SOPten(flox/flox)(P21-27) mice] developed spontaneous lung adenocarcinomas. Urethane treatment accelerated number and size of lung tumors developing in SOPten(flox/flox) mice of both ages. Histological and biochemical examinations of the lungs of SOPten(flox/flox)(E10-16) mice revealed hyperplasia of bronchioalveolar epithelial cells and myofibroblast precursors, enlarged alveolar epithelial cells, and impaired production of surfactant proteins. Numbers of bronchioalveolar stem cells (BASCs), putative initiators of lung adenocarcinomas, were increased. Lungs of SOPten(flox/flox)(E10-16) mice showed increased expression of Spry2, which inhibits the maturation of alveolar epithelial cells. Levels of Akt, c-Myc, Bcl-2, and Shh were also elevated in SOPten(flox/flox)(E10-16) and SOPten(flox/flox)(P21-27) lungs. Furthermore, K-ras was frequently mutated in adenocarcinomas observed in SOPten(flox/flox)(P21-27) lungs. These results indicate that Pten is essential for both normal lung morphogenesis and the prevention of lung carcinogenesis, possibly because this tumor suppressor is required for BASC homeostasis. [ABSTRACT FROM AUTHOR]

Published
2007
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