Expression data from GNMT knockout mice

We report that 7 of 7 female Gnmt-/- mice developed hepatocellular carcinoma (HCC), the most common form of liver cancer, at the mean age of 16.1 months. In contrast, only one-third (2/6) of male Gnmt-/- mice had HCC, the remaining had either premature death or liver necrosis. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: S-adenosylmethionine (SAM)-dependent methyltransferases, metabolism, signal transduction, cell proliferation, cell adhesion and immune responses. This study reveals that GNMT plays an important role in the prevention of hapatotumorigenesis through regulating DNA methylaiton and oxidative stress signaling pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Keywords: Gnmt knockout Liver tissues from wild-type or Gnmt knockout mice at young ages, developing dysplasia nodules or HCC were used for RNA extraction and hybridization on Affymetrix microarrays. For 11 weeks old mice, total RNA were mixed in equal proportion from 3 mice.本研究显示，7只雌性GNMT敲除（Gnmt-/-）小鼠均在平均16.1月龄时罹患肝细胞癌（hepatocellular carcinoma，HCC），该病症为最常见的肝癌类型。与之相比，仅有三分之一（2/6）的雄性GNMT敲除小鼠罹患HCC，其余小鼠或过早死亡，或出现肝坏死。基因芯片（microarray）分析显示，在肿瘤发生的不同阶段，参与下述通路的基因存在表达失调情况：S-腺苷甲硫氨酸（S-adenosylmethionine，SAM）依赖型甲基转移酶、代谢、信号转导、细胞增殖、细胞黏附以及免疫应答相关通路。本研究揭示，GNMT通过调控DNA甲基化与氧化应激信号通路，在预防肝肿瘤发生过程中发挥重要作用。本研究推测，GNMT属于应激响应蛋白，其表达水平或可解释肝癌易感性的性别差异。关键词：采用年轻野生型或GNMT敲除小鼠、存在发育异常结节或HCC的小鼠的肝组织进行RNA提取，并在Affymetrix基因芯片上完成杂交实验；对于11周龄的小鼠，将3只小鼠的总RNA按等比例混合。