Thesis

Liver cancer chemoprevention : transcriptional regulation of AKR7A1 dietary chemoprevention

Creator
Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T14057
Person Identifier (Local)
  • 201363044
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Chemoprevention is best defined as the use of chemical agents to inhibit, retard or reverse the process of tumorigenesis. Many of these agents are present in the diet, with consequent public health benefits. It has been shown in previous studies that certain chemoprotective agents can protect the liver from hepatocarcinogenesis initiated by aflatoxin B1 through up-regulating the expression of genes encoding protective enzymes. This is mediated through the transcription factor Nrf2 binding to an antioxidant response element (ARE) in the promoter region of responsive genes. One of the most responsive genes encodes the aldo-keto reductase AKR7A1, which detoxifies aflatoxin B1 dialdehyde. The main objective of this study was to investigate the sequences within the AKR7A1 promoter that make it so responsive to dietary chemoprotectors. In particular the 4000 bp promoter region was studied in variety of promoter fusions with the reporter gene luciferase, and expression was examined in rat liver cells. This project identified regions of the promoter that affect AKR7A1 gene expression while also uncovering new information about the putative ARE transcription factor binding sites within the promoter.
Resource Type
DOI
Date Created
  • 2014
Former identifier
  • 1231458

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