Molecular cross-talk between the TRAIL and interferon signaling pathways.

Abstract

TRAIL/APO-2L induces apoptosis in a variety of transformed cells and has potential as an anti-cancer therapeutic. The physiologic role of TRAIL is presumably more complex than merely activating caspase-mediated cell death. To shed light into TRAIL-mediated signaling, we used DNA microarrays to profile gene expression mediated by TRAIL in breast carcinoma cells. Primary response genes induced by TRAIL included a number of known NF-kappaB-dependent genes such as cIAP2, A20, and E-selectin. Remarkably, global transcriptome analysis revealed that TRAIL also induced a cohort of genes related to the interferon-signaling pathway. Assessing interferon-induced gene expression suggested various points of interaction with the TRAIL signaling pathway. Interestingly, while we observed interferon-mediated up-regulation of TRAIL, we also demonstrated a concomitant TRAIL-mediated induction of interferon-beta. Combining TRAIL and interferon in vitro, synergistically induced apoptosis and caspase activation in breast cancer cells. Together, these data indicate multiple levels of molecular cross-talk between the two diverse cytokines with anti-tumor properties.

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@article{KumarSinha2002MolecularCB, title={Molecular cross-talk between the TRAIL and interferon signaling pathways.}, author={Chandan Kumar-Sinha and Sooryanarayana Varambally and Arun Sreekumar and Arul M. Chinnaiyan}, journal={The Journal of biological chemistry}, year={2002}, volume={277 1}, pages={575-85} }