Structure and promoter characterization of aldo-keto reductase family 1 B10 gene.
Structure and promoter characterization of aldo-keto reductase family 1 B10 gene.
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DOI：
10.1016/j.gene.2009.02.007
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发表时间：
2009-05-15
期刊：
影响因子：
3.5
通讯作者：
Cao D
中科院分区：
文献类型：
--
作者：
Liu Z;Zhong L;Krishack PA;Robbins S;Cao JX;Zhao Y;Chung S;Cao D
醛酮还原酶家族1成员B10（AKR 1B 10）在吸烟者的肝细胞癌、肺鳞癌和肺腺癌中过表达。我们最近的研究表明，AKR 1B 10通过解毒活性羰基和调节脂肪酸生物合成在癌细胞的生长和增殖中起着关键作用。然而，关于AKR 1B 10表达的调控机制知之甚少。本研究测定了AKR 1B 10基因的结构，并对其启动子进行了鉴定。结果表明，AKR 1B 10基因由10个外显子和9个内含子组成，全长约13.8kb。5′-RACE研究确定AKR 1B 10的转录起始位点在ATG翻译起始密码子上游320 bp处。TATA样（TAATAA）和CAAT盒分别存在于转录起始位点上游的-145至-140 bp和-193至-190 bp处。AKR 1B 10基因启动子5′端的一个约4, 091 bp的片段能够驱动GFP和荧光素酶报告基因在人肝癌细胞HepG 2中表达;进行性5′-缺失显示-255 bp片段具有完全启动子活性。
Aldo-keto reductase family 1 member B10 (AKR1B10) is overexpressed in human hepatocellular carcinoma, lung squamous carcinoma, and lung adenocarcinoma in smokers. Our recent studies have showed that AKR1B10 plays a critical role in the growth and proliferation of cancer cells by detoxifying reactive carbonyls and regulating fatty acid biosynthesis. However, little is known about the regulatory mechanisms of AKR1B10 expression. In this study, we determined the structure of AKR1B10 gene and characterized its promoter. The results demonstrated that AKR1B10 consists of 10 exons and 9 introns, stretching approximately 13.8 kb. A 5′-RACE study determined the transcriptional start site of AKR1B10 at 320 bp upstream of the ATG translational start codon. A TATA-like (TAATAA) and a CAAT box are present from −145 to −140 bp and −193 to −190 bp upstream of the transcriptional start site, respectively. Motif analysis recognized multiple putative oncogenic and tumor suppressor protein binding sites in the AKR1B10 promoter, including c-Ets-1, C/EBP, AP-1, and p53, but osmolytic response elements were not found. A -4,091 bp of the 5′-flanking fragment of the AKR1B10 gene was capable of driving GFP and luciferase reporter gene expression in HepG2 cells derived from human hepatocellular carcinoma; progressive 5′-deletions revealed that a −255 bp fragment possesses full promoter activity.
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