Thesis

Cancer chemoprevention : transcriptional regulation of AKR7A1 by dietary chemoprotectors

Creator
Awarding institution
  • University of Strathclyde
Date of award
  • 2012
Thesis identifier
  • T13619
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Chemoprevention is a process of preventing initiation of carcinogenesis with the help of chemicals found in the diet. In previous studies, it was found that the process involved up-regulation of chemoprotective genes such as AKR7A1, mediated by oxidative response proteins such as Nrf2, binding to the Antioxidant Response Elements (ARE) in the promoter region of AKR7A1. Previously, putative ARE sequences were detected in AKR7A1 promoter region. The main objective of this study was to investigate the presence of more ARE sequences in the distal promoter regions and to depict a vivid image of the chemoprotection mechanism which was not clearly understood before. To do so, several experiments were undertaken, such as, "Motif Overrepresentation Analysis" to detect putative Nrf2 binding site/ ARE in the 4kb promoter region, "Expression of deletion constructs ligated into reporter vectors" to assess the induction capacity of promoter having different length in presence of tert-butylhydroquinone (TBHQ) and "Single Nucleotide Mutagenesis study" to confirm the specific Nrf2 binding site within the promoter region. The results of "Motif overrepresentation Analysis" showed the presence of several Antioxidant Response Elements (ARE) in both proximal and distal regions of AKR7A1 promoter relative to the Transcription Starting Site (TSS). Results found in the bioinformatic analysis were seconded by the "Deletion study" and specific Nrf2 binding sites were confirmed by the data found in "Site specific mutagenesis study".
Resource Type
DOI
Date Created
  • 2012
Former identifier
  • 1004015

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