Amann Thomas, Kirovski Georgi, Bosserhoff Anja Kathrin, Hellerbrand Claus
Department of Internal Medicine I, University Hospital Regensburg, Regensburg.
Mol Membr Biol. 2011 Apr;28(3):182-6. doi: 10.3109/09687688.2011.554447. Epub 2011 Feb 18.
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.
葡萄糖转运蛋白异构体1（GLUT1）是癌细胞中葡萄糖运输和代谢的关键限速因子。最近，我们发现GLUT1在肝细胞癌（HCC）中表达增加，并促进HCC细胞的致瘤性。缺氧进一步增加了HCC细胞中GLUT1的表达，这种诱导依赖于转录因子缺氧诱导因子（HIF）-1α的激活。GLUT1基因的启动子区域存在一个单核苷酸多态性（SNP；Rs710218；-2841处A到T），与一个假定的HIF-1α结合位点紧密相邻，最近发现该SNP在肾细胞癌患者中更为常见。在本研究中，HCC患者（n = 95；AA：60%；AT 36%；TT：4%）和健康对照者（n = 127；AA：50%；AT 41%；TT：9%）之间A-2841T基因型分布没有显著差异。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的GLUT1表达水平较高，并且倾向于显示出更具侵袭性的肿瘤生长。这些数据表明，SNP Rs710218与HCC的较高风险无关，而是与HCC进展有关，可能是通过HIF-1α介导的GLUT1表达增加。
