Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not Only Causes apoptotic cell death in tumor cells, but also activates some transcription factors and affects several other cellular functions. In this study, we observed the effect of administration of TRAIL on gene expression downstream of the cyclic AMP responsive element (CRE) enhancer by using the signal transduction reporter cis-element plasmid pCRE-d2EGFP. Western blotting showed that after administration of TRAIL, the expression level of reporter protein d2EGFP was down-regulated in NIH3T3 cells. To confirm the TRAIL-induced down-regulation of CRE enhancer controlled gene expression, DNA Chip time series analysis of the intrinsic genes expressed in NIH3T3 cells was carried out. As a result, the expression levels of six genes, which have CRE sequence in their promoter region, were slightly down-regulated within three hours after administration of TRAIL. (C) 2009 Elsevier Inc. All rights reserved