Analysis of the TLR/NF-kappaB pathway in antigen-presenting cells in malignancies promoted by inflammation

Abstract

Activation of the transcription factor, nuclear factor of kappaB (NF-kappaB), has recently emerged as the critical link between inflammation and cancer. NF-kappaB is activated by many signals including DNA damage and microbial pathogen recognition. Although microbial infections account for an estimated 15% of all cancer related deaths, NF-kappaB is constitutively activated in various types of cancer as a direct result of chromosomal translocations, deletions and mutations affecting both NF-kappaB and its regulators. NF-kappaB exerts the transcriptional activation and repression of inflammatory and immune response genes as well as genes mediating cell survival and proliferation, and thus stands to impact various cellular processes. The decision is made through the integration of the pathway of NF-kappaB activation with a complex array of cell signaling networks that are at present poorly understood. Here, two methods are presented, protein co-immunoprecipitation and subcellular co-localization by immunofluorescence microscopy, to help investigations into the links between NF-kappaB-induced inflammation and cancer. Understanding the details of these pathways will aid in the development of new diagnostic and therapeutic applications.