Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma
Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma
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DOI：
10.1016/j.ejca.2004.12.037
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发表时间：
2005-06-01
影响因子：
8.4
通讯作者：
Yamada, N
中科院分区：
文献类型：
--
作者：
Yahagi, N;Shimano, H;Yamada, N
肝细胞癌是B和/或C型肝炎病毒流行的国家中非常常见的肿瘤性疾病。早期超声检查发现的小肝癌病灶通常是高回声的，因为它们由富含甘油三酯滴的分化良好的癌细胞组成。肝细胞的甘油三酯含量部分取决于脂肪生成的速率。关键的脂肪生成酶，如脂肪酸合成酶，在转录水平上协同调节。因此，我们研究了10例接受手术切除的人肝细胞癌样本中脂肪生成酶的mRNA表达。与周围的非癌肝组织相比，所有样品都表现出脂肪生成酶（如脂肪酸合成酶、乙酰辅酶A羧化酶和ATP柠檬酸裂解酶）的mRNA表达的显著升高。相反，SREBP-1（一种调节脂肪生成酶的转录因子）mRNA表达的变化没有显示出一致的趋势。在SREBP-1升高的某些情况下，主要的贡献亚型是SREBP-1c而不是SREBP-1a。因此，在肝细胞癌中显着诱导脂肪生成酶，在某些情况下，SREBP-1c参与这种激活。(c)2005爱思唯尔有限公司保留所有权利。
Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation. (c) 2005 Elsevier Ltd. All rights reserved.