Ad-IRF-1 induces apoptosis in esophageal adenocarcinoma.

Journal Article (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

  • PMC1584287

Electronic International Standard Serial Number (EISSN)

  • 1476-5586

Digital Object Identifier (DOI)

  • 10.1593/neo.05559


  • eng

Conference Location

  • United States