Structure and promoter characterization of aldo-keto reductase family 1B10 gene

Department of Medical Microbiology, Immunology, and Cell Biology, SimmonsCooper Cancer Institute, Southern Illinois University School of Medicine, 913 N. Rutledge Street, Springfield, IL 62702, USA.
Gene (Impact Factor: 2.08). 03/2009; 437(1-2):39-44. DOI: 10.1016/j.gene.2009.02.007
Source: PubMed

ABSTRACT 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 -4091 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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Available from: Linlin Zhong, Aug 27, 2014
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    • "The cancer-associated overexpression of AKR1B10 probably results from an adaptive response to oncogenic processes, but little is known about its gene regulation. Liu et al. (2009b) characterized the promoter region of the AKR1B10 gene, which includes multiple putative oncogenic and tumor suppressor protein binding sites, including the transcriptional factors c-Ets-1 and C/EBP, the repressor protein p53, and the AP-1 oncogene. Nishinaka et al. (2011) identified several putative regulatory motifs, such as AP- 1, NF-κB, and antioxidant response element, in a −3282 bp of the 5 -flanking region and 5 -untranslation region of AKR1B10 gene, and also suggest a possibility that a complex polymorphic microsatellite in this region is implicated in the enzyme induction in response to certain stimuli such as carcinogens. "
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