Nrf2 and chemoprevention: Signaling, epigenetics and role in intestinal tumorigenesis.

摘要

Prevention is better than cure. The carcinogenesis could take as long as 20 to 30 years to develop from initiated cells to malignant tumor, therefore providing us various opportunities to prevent the appearance of tumors with the use of chemopreventive compounds in the early stage. Chemoprevention becomes an increasing important concept and has led to the intense research about the mechanisms of actions of various chemopreventive compounds. They can be generally classified into blocking agents and suppressing agents. The chemopreventive compounds usually prevent or slow progression of cancer by maintaining a low oxidative stress and inflammatory environment in cells. This is brought about by the activation of Nrf2, the key protein being investigated in our lab. In this dissertation, I will be discussing the use of compounds as suppressing agents and blocking agents, how compounds activates Nrf2 signaling, how novel Nrf2 interaction partner IQGAP1 mediates Nrf2-Keap1 signaling axis, how expression level of Nrf2 could be regulated epigenetically, apart from the well-known post-translational control by Keap1-Ubiquitinase-Protesome axis and finally how loss of Nrf2 could enhance intestinal tumorigenesis in Apc(min/+) mice.