Santamaría Enrique, Muñoz Javier, Fernandez-Irigoyen Joaquín, Sesma Laura, Mora María I, Berasain Carmen, Lu Shelly C, Mato José M, Prieto Jesús, Avila Matías A, Corrales Fernando J
Division of Hepatology and Gene Therapy, CIMA, University of Navarra, 31008 Pamplona, Spain.
J Proteome Res. 2006 Apr;5(4):944-53. doi: 10.1021/pr050429v.
S-adenosylmethionine arises as a central molecule in the preservation of liver homeostasis as a chronic hepatic deficiency results in spontaneous development of steatohepatitis and hepatocellular carcinoma. In the present work, we have attempted a comprehensive analysis of proteins associated with hepatocarcinogenesis in MAT1A knock out mice using a combination of two-dimensional electrophoresis and mass spectrometry, to then apply the resulting information to identify hallmarks of human HCC. Our results suggest the existence of individual-specific factors that might condition the development of preneoplastic lesions. Proteomic analysis allowed the identification of 151 differential proteins in MAT1A-/- mice tumors. Among all differential proteins, 27 changed in at least 50% of the analyzed tumors, and some of these alterations were already detected months before the development of HCC in the KO liver. The expression level of genes coding for 13 of these proteins was markedly decreased in human HCC. Interestingly, seven of these genes were also found to be down-regulated in a pretumoral condition such as cirrhosis, while depletion of only one marker was assessed in less severe liver disorders.
S-腺苷甲硫氨酸作为维持肝脏内环境稳定的核心分子而存在，因为慢性肝脏缺乏会导致脂肪性肝炎和肝细胞癌的自发发展。在本研究中，我们尝试结合二维电泳和质谱法对MAT1A基因敲除小鼠中与肝癌发生相关的蛋白质进行全面分析，然后将所得信息应用于识别人类肝癌的特征。我们的结果表明存在可能影响癌前病变发展的个体特异性因素。蛋白质组学分析在MAT1A-/-小鼠肿瘤中鉴定出151种差异蛋白质。在所有差异蛋白质中，27种在至少50%的分析肿瘤中发生变化，其中一些变化在基因敲除肝脏中肝癌发生前几个月就已被检测到。在人类肝癌中，编码这些蛋白质中13种的基因表达水平显著降低。有趣的是，在诸如肝硬化等肿瘤前状态中也发现其中7个基因下调，而在不太严重的肝脏疾病中仅评估了一种标志物的缺失情况。
