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- W1784451823 abstract "Up-regulation of cyclooxygenase-2 (COX-2) is an early and key event in human colorectal carcinogenesis (CRC). Nevertheless, the molecular mechanisms leading to this over-expression are largely unknown. We previously reported an association between the -1195G allele and higher predisposition for CRC in a Caucasian population. The biological explanation for the involvement of this polymorphism in CRC remains elusive. We aimed to functionally characterize the influence of the -1195A>G promoter region polymorphism on COX-2 transcription activity in colon cancer cell lines. Luciferase reporter assays were performed to assess whether the -1195A/G alleles influenced COX-2 transcription. The COX-2 promoter's region containing either the -1195A or -1195G alleles was cloned into pGL3-basic reporter vector. The reporter vectors were transiently co-transfected with the pGL4.73 control plasmid to HCT-116 and HCA-7 colon cancer cell lines. The levels of reporter gene expression driven by the -1195G allele-containing COX-2 promoter were significantly higher in both colon cancer cell lines. A 2.2-fold increase in promoter activity was observed in the HCT-116 cell line (P < 0.001), and this over-expression was even more noticeable in the HCA-7 COX-2 expressing cell line with a threefold higher transcriptional activity (P = 0.001). The -1195G allele appeared to enhance COX-2 transcription, providing a molecular basis underlying the increased susceptibility for CRC and potentially a new mechanism for COX-2 overexpression." @default.
- W1784451823 created "2016-06-24" @default.
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- W1784451823 date "2013-06-18" @default.
- W1784451823 modified "2023-09-26" @default.
- W1784451823 title "The −1195G allele increases the transcriptional activity of cyclooxygenase-2 gene (COX-2) in colon cancer cell lines" @default.
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- W1784451823 doi "https://doi.org/10.1002/mc.22049" @default.
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