IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-02

AUTHORS

Peter K M Kim, Michaele Armstrong, Ye Liu, Peng Yan, Brian Bucher, Brian S Zuckerbraun, Andrea Gambotto, Timothy R Billiar, John H Yim

ABSTRACT

Interferon regulatory factor-1 (IRF-1) is a nuclear transcription factor that mediates interferon and other cytokine effects and appears to have antitumor activity in vitro and in vivo in cancer cells. We have constructed a recombinant adenoviral vector (Ad-IRF-1) that infects mammary cells with high efficiency and results in high levels of functional IRF-1 protein in transfected cells. Overexpression of IRF-1 in two mouse breast cancer cell lines, C3-L5 and TS/A, resulted in apoptosis in these cell lines as assessed by Annexin V staining. The involvement of caspases was confirmed by significant inhibition of apoptosis by a caspase inhibitor, and by demonstration of caspase-3 activity, cleavage of caspase-3, and PARP cleavage. Interestingly, the growth of nonmalignant breast cell lines C127I and NMuMG did not appear to be inhibited by IRF-1 overexpression. Suppression of growth for breast cancer cell lines in vivo was demonstrated by both preinfection of breast cancer cells ex vivo and by intratumoral injection of Ad-IRF-1 into established tumors in their natural hosts. The mechanism of apoptosis may involve the transcriptional upregulation of bak, caspase-8, and caspase-7 expression. These data support the antitumor potential of IRF-1 and the use of agents that increase IRF-1 in breast cancer. More... »

PAGES

1125

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1207023

    DOI

    http://dx.doi.org/10.1038/sj.onc.1207023

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1004159540

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/14762441


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