Ad-IRF-1 induces apoptosis in esophageal adenocarcinoma.
Journal Article
The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppressor, but the expression and function of IRF-1 in esophageal adenocarcinoma (EA) remain unknown. We hypothesized that IRF-1 expression was reduced or lost in EA and that restoration of IRF-1 would result in the apoptosis of EA cells in vitro and the inhibition of tumor growth in vivo. Three EA cell lines were used to examine IRF-1 expression, IFN-gamma responsiveness, and the effects of IRF-1 overexpression using a recombinant adenoviral vector (Ad-IRF-1). All three EA cell lines produced IRF-1 protein following IFN-gamma stimulation, although IFN-gamma did not induce cell death. In contrast, Ad-IRF-1 infection resulted in high levels of IRF-1 protein and triggered apoptosis in all three EA cell lines. Potential mechanisms for the differential response to IFN-gamma versus Ad-IRF-1--such as modulation of c-Met or extracellular regulated kinase signaling, or altered expression of IRF-2, Fas, or survivin--were investigated, but none of these mechanisms can account for this observation. In vivo administration of IRF-1 in a murine model of EA modestly inhibited tumor growth, but did not lead to tumor regression. Strategies aimed at increasing or restoring IRF-1 expression may have therapeutic benefits in EA.
Full Text
Duke Authors
Cited Authors
- Watson, GA; Queiroz de Oliveira, PE; Stang, MT; Armstrong, MJ; Gooding, WE; Kuan, S-F; Yim, JH; Hughes, SJ
Published Date
- January 2006
Published In
Volume / Issue
- 8 / 1
Start / End Page
- 31 - 37
PubMed ID
- 16533423
Pubmed Central ID
- 16533423
Electronic International Standard Serial Number (EISSN)
- 1476-5586
Digital Object Identifier (DOI)
- 10.1593/neo.05559
Language
- eng
Conference Location
- United States