Role of c-myc in the Tumor Promoting Actions of Oxidized Lipids in the Colon
The research in our lab investigates the mechanisms of cancer progression, focusing on the control of gene expression and its role in driving cancer growth. The transcription factor c-myc is a protein which controls the ‘turning on’ or ‘turning off’ of many genes, and the dysregulation of c-myc is observed in many cancer types. Although it can enhance the proliferation of cancer cells, high levels of c-myc can paradoxically sensitize cancer cells to pro-apoptotic stimuli, and therefore limit tumor growth. We studied c-myc regulation in the context of oxidized lipids, which are commonly elevated in the inflammatory environment of solid tumors. We use 4-hydroxynonenal (HNE) as a model is compound in our studies. HNE a reactive lipid that is generated as a consequence of localized inflammation and oxidative stress, and HNE is found to be elevated in and around solid tumors. Our studies have shown that HNE enhances the expression and activity of c-myc in colorectal cancer cells. We have studied the consequence of this increase in c-myc expression following HNE treatment and found that it has a role in promoting apoptotic cell death. Our interest now is in better defining the mechanism by which c-myc promotes cell death in HNE-treated cancer cells, including the genes and signaling pathways involved. Overall, we believe our research may provide a better understanding of how localized inflammation and the generation of oxidized lipids can keep cancer growth in-check.