Article

Structure and promoter characterization of aldo-keto reductase family 1 B10 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: 2.34). 03/2009; 437(1-2):39-44. DOI:10.1016/j.gene.2009.02.007 pp.39-44
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.

0 0
 · 
0 Bookmarks
 · 
43 Views
  • Source
    Article: Pro-oncogene Pokemon promotes breast cancer progression by upregulating survivin expression.
    Xuyu Zu, Jun Ma, Hongxia Liu, Feng Liu, Chunyan Tan, Lingling Yu, Jue Wang, Zhenhua Xie, Deliang Cao, Yuyang Jiang
    [show abstract] [hide abstract]
    ABSTRACT: Pokemon is an oncogenic transcription factor involved in cell growth, differentiation and oncogenesis, but little is known about its role in human breast cancer. In this study, we aimed to reveal the role of Pokemon in breast cancer progression and patient survival and to understand its underlying mechanisms. Tissue microarray analysis of breast cancer tissues from patients with complete clinicopathological data and more than 20 years of follow-up were used to evaluate Pokemon expression and its correlation with the progression and prognosis of the disease. DNA microarray analysis of MCF-7 cells that overexpress Pokemon was used to identify Pokemon target genes. Chromatin immunoprecipitation (ChIP) and site-directed mutagenesis were utilized to determine how Pokemon regulates survivin expression, a target gene. Pokemon was found to be overexpressed in 158 (86.8%) of 182 breast cancer tissues, and its expression was correlated with tumor size (P = 0.0148) and lymph node metastasis (P = 0.0014). Pokemon expression led to worse overall (n = 175, P = 0.01) and disease-related (n = 79, P = 0.0134) patient survival. DNA microarray analyses revealed that in MCF-7 breast cancer cells, Pokemon regulates the expression of at least 121 genes involved in several signaling and metabolic pathways, including anti-apoptotic survivin. In clinical specimens, Pokemon and survivin expression were highly correlated (n = 49, r = 0.6799, P < 0.0001). ChIP and site-directed mutagenesis indicated that Pokemon induces survivin expression by binding to the GT boxes in its promoter. Pokemon promotes breast cancer progression by upregulating survivin expression and thus may be a potential target for the treatment of this malignancy.
    Breast cancer research: BCR 03/2011; 13(2):R26. · 5.24 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

-255 bp fragment possesses full promoter activity
 
AKR1B10 expression
 
AKR1B10 promoter
 
Aldo-keto reductase family 1 member B10
 
AP-1
 
ATG translational start codon
 
c-Ets-1
 
CAAT box
 
critical role
 
detoxifying reactive carbonyls
 
human hepatocellular carcinoma
 
luciferase reporter gene expression
 
Motif analysis
 
multiple putative oncogenic
 
progressive 5'-deletions
 
recent studies
 
transcriptional start site
 
tumor suppressor protein binding sites