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- Title
IRF-1 expression induces apoptosis and inhibits tumor growth in mouse mammary cancer cells in vitro and in vivo.
- Authors
Armstrong, Michaele; Ye Liu; Peng Yan; Bucher, Brian; Gambotto, Andrea; Kim, Peter K. M.; Zuckerbraun, Brian S.; Billiar, Timothy R.; Yim, John H.
- 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.Oncogene (2004) 23, 1125-1135. doi:10.1038/sj.onc.1207023
- Subjects
TRANSCRIPTION factors; INTERFERONS; APOPTOSIS; CELL lines; BREAST cancer; CANCER cells; GENETIC transcription; TUMOR growth
- Publication
Oncogene, 2004, Vol 23, Issue 5, p1125
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207023