Analysis of a promoter polymorphism of the GLUT1 gene in patients with hepatocellular carcinoma
Analysis of a promoter polymorphism of the GLUT1 gene in patients with hepatocellular carcinoma
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DOI：
10.3109/09687688.2011.554447
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发表时间：
2011-04-01
影响因子：
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通讯作者：
Hellerbrand, Claus
中科院分区：
文献类型：
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作者：
Amann, Thomas;Kirovski, Georgi;Hellerbrand, Claus
葡萄糖转运蛋白亚型1（GLUT 1）是癌细胞中葡萄糖转运和代谢的关键限速因子。最近，我们发现GLUT 1在肝细胞癌（HCC）中表达增加，并促进HCC细胞的致瘤性。缺氧进一步增加肝癌细胞中GLUT 1的表达，这种诱导依赖于转录因子缺氧诱导因子（HIF）-1 α的激活。GLUT 1基因的启动子区具有一个单核苷酸多态性（SNP; Rs710218;-2841处A至T），该多态性靠近推定的HIF-1 α结合位点，最近发现该SNP在肾细胞癌患者中更常见。在本研究中，A-2841 T基因型分布在HCC患者（n = 95; AA：60%; AT 36%和TT：4%）和健康对照组（n = 127; AA：50%; AT 41%和TT：9%）之间没有显著差异。然而，值得注意的是，T等位基因的非携带者在癌性肝组织中具有更高的GLUT 1表达水平，并且倾向于揭示更具侵略性的肿瘤生长。这些数据表明，SNP Rs710218与HCC的高风险无关，而是与HCC进展相关，可能通过HIF-1 α介导的GLUT 1表达增加。
The glucose transporter isoform 1 (GLUT1) is a key rate-limiting factor in the transport and metabolism of glucose in cancer cells. Recently, we found that GLUT1 expression is increased in hepatocellular carcinoma (HCC) and promotes tumorigenicity of HCC cells. Hypoxia further increased GLUT1 expression in HCC cells, and this induction was dependent on the activation of the transcription factor hypoxia-inducible factor (HIF)-1alpha. The promoter region of the GLUT1 gene harbors a single nucleotide polymorphism (SNP; Rs710218; A to T at -2841) closely positioned to a putative HIF-1alpha binding site, and recently, this SNP was found to be more frequent in patients with renal cell carcinoma. In the present study, the A-2841T genotype distribution did not differ significantly between HCC patients (n == 95; AA: 60%; AT 36% and TT: 4%) and healthy controls (n == 127; AA: 50%; AT 41% and TT: 9%). However and noteworthy, non-carriers of the T allele had higher GLUT1 expression levels in cancerous hepatic tissue, and tended to reveal a more aggressive tumour growth. These data indicate that the SNP Rs710218 is not associated with a higher risk for HCC but rather for HCC progression, potentially via HIF-1alpha mediated increased GLUT1 expression.