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  • Original Paper
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IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo

Oncogene volume 23, pages 1125–1135 (2004)Cite this article

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.

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Acknowledgements

We thank Dr Walter Storkus for helpful advice. We thank Ms Yun Hua for her technical expertise and Dr Jianhua Luo for assistance with the microarray analysis. Northern probe for caspase-8 was a generous gift from Dai-Wu Seol. This work was supported by the American College of Surgeons Faculty Fellowship (JHY), the Pittsburgh Foundation (JHY), the Society of Surgical Oncology (PKMK), and the American College of Surgeons (PKMK).

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  1. Department of Surgery, University of Pittsburgh Medical Center, 497 Scaife Hall, 3550 Terrace Street, Pittsburgh, 15261, PA, USA

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

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  1. Peter K M Kim
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Correspondence to John H Yim.

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Kim, P., Armstrong, M., Liu, Y. et al. IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo. Oncogene 23, 1125–1135 (2004). https://doi.org/10.1038/sj.onc.1207023

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