The expression of the Adenovirus serotype 5 (Ad5) E1A oncogene sensitizes tumor cells to natural killer (NK) cell–mediated killing and tumor rejection in vivo. These effects are dependent on the ability of E1A to bind the transcriptional coadaptor protein p300. To test the hypothesis that E1A up-regulates ligands recognized by the NKG2D-activating receptor, we stably transfected the highly tumorigenic mouse fibrosarcoma cell line MCA-205 with Ad5-E1A or a mutant form of E1A that does not interact with p300 (E1A-Δp300). Ad5-E1A, but not E1A-Δp300, up-regulated the expression of the NKG2D ligand retinoic acid early inducible (RAE)-1, but not murine ULBP-like transcript 1, another NKG2D ligand, in four independently derived MCA-205 transfectants. The up-regulation of RAE-1 by E1A targeted MCA-205 tumor cells to lysis by NK cells, resulting in NKG2D-dependent tumor rejection in vivo. Moreover, the up-regulation of NKG2D ligands by E1A was not limited to mouse tumor cells, as E1A also increased the expression of NKG2D ligands on primary baby mouse kidney cells, human MB435S breast cancer cells, and human H4 fibrosarcoma cells.
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5 December 2005
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November 28 2005
Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection
John M. Routes,
John M. Routes
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
2Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
3Cancer Center, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
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Sharon Ryan,
Sharon Ryan
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
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Kristin Morris,
Kristin Morris
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
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Rayna Takaki,
Rayna Takaki
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
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Adelheid Cerwenka,
Adelheid Cerwenka
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
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Lewis L. Lanier
Lewis L. Lanier
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
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John M. Routes
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
2Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
3Cancer Center, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
Sharon Ryan
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
Kristin Morris
1Integrated Department of Immunology, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80262
Rayna Takaki
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
Adelheid Cerwenka
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
Lewis L. Lanier
4Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143
CORRESPONDENCE John M. Routes: [email protected]
Abbreviations used: Ad, adenovirus; BMK, baby mouse kidney; HPV, human papillomavirus; MULT1, murine ULBP-like transcript 1; RAE, retinoic acid early inducible; Rb, retinoblastoma.
A. Cerwenka's present address is Deutsches Krebsforschungszentrum, DKFZ, 69120 Heidelberg, Germany.
Received:
January 28 2005
Accepted:
October 20 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 202 (11): 1477–1482.
Article history
Received:
January 28 2005
Accepted:
October 20 2005
Citation
John M. Routes, Sharon Ryan, Kristin Morris, Rayna Takaki, Adelheid Cerwenka, Lewis L. Lanier; Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection . J Exp Med 5 December 2005; 202 (11): 1477–1482. doi: https://doi.org/10.1084/jem.20050240
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