Hepatocellular carcinoma caused by loss of heterozygosity in Lkb1 gene knockout mice

作者: Masayuki Nakau , Masanobu Oshima , Masayuki Imamura , Makoto M. Taketo , Michael F. Seldin

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摘要: Germline mutations of the LKB1 gene are associated with Peutz-Jeghers syndrome, which is characterized by mucocutaneous pigmentation and gastrointestinal hamartoma an increased risk cancer development. To investigate role in vivo, we have recently constructed Lkb1 knockout mice. Because haploinsufficiency, heterozygous mice develop polyps histological characteristics resemble those syndrome hamartomas. Here demonstrate that (+/-) hepatocellular carcinomas (HCCs). In >50 weeks age, >70% male developed HCCs, whereas only 20% females had showing a sex difference susceptibility. Histological examinations revealed various types such as "trabecular," "clear cell," "pseudoglandular," "sarcomatous" types, were strikingly similar to found human HCCs. Western blotting PCR analyses showed loss heterozygosity all HCC tissues examined, indicating tumor suppressor mouse liver. These results suggest lack novel mechanism for Thus, mutant should be important useful model HCC.

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