Assessment of tumor necrosis factor receptor and fas signaling pathways bytranscriptional profiling

Apoptosis, or programmed cell death, Is an important mechanism by which cel ls are eliminated during immune regulation and embryonic development. Aberr ations in the signaling pathways leading to apoptosis may result in cancer, autoimmune diseases, or inflammatory disorders. In view of this, an unders tanding of the signaling capabilities of apoptosis-inducing or death recept ors is essential to understanding their roles in biology and disease. We us ed cDNA microarrays to examine the downstream transcriptional effects of tw o members of the tumor necrosis factor (TNF) family of death receptor ligan ds, We compared the transcriptional responses of a model colon cancer cell line, HT29, to TNF-alpha and anti-Fas activating antibody. Both ligands ind uced a subset of genes characteristic of activation of the transcription fa ctor nuclear factor-kappaB (NF-kappaB). Follow-up analyses demonstrated tha t, although TNF-alpha activated NF-kappaB through I kappaB-alpha degradatio n, alpha -Fas treatment led to NF-kappaB activation through a mechanism dis tinct from I kappaB-alpha degradation.