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Adenovirus E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis-Inducing Ligand (TRAIL)

John M. Routes, Sharon Ryan, Amanda Clase, Tanya Miura, Alicia Kuhl, Terry A. Potter and James L. Cook
J Immunol October 15, 2000, 165 (8) 4522-4527; DOI: https://doi.org/10.4049/jimmunol.165.8.4522
John M. Routes
*Medicine and
†Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206; Departments of
‡Medicine,
§Immunology, and the
¶Cancer Center, University of Colorado Medical School, Denver, CO 80262; and
∥Department of Medicine and Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612
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Sharon Ryan
*Medicine and
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Amanda Clase
*Medicine and
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Tanya Miura
*Medicine and
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Alicia Kuhl
*Medicine and
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Terry A. Potter
†Immunology, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206; Departments of
§Immunology, and the
¶Cancer Center, University of Colorado Medical School, Denver, CO 80262; and
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James L. Cook
∥Department of Medicine and Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612
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  • FIGURE 1.
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    FIGURE 1.

    E1A-transfected, but not Ad5-infected, human tumor cells are sensitive to TRAIL-induced lysis. A2058 and A2058-E1A are parental and E1A-transfected, human melanoma cells, respectively. H4 and H4-E1A are parental and E1A-transfected fibrosarcoma cells. A, TRAIL-induced lysis of A2058 (○), Ad5-infected-A2058 (•), or A2058-E1A (▪) cells. B, TRAIL-induced killing of H4 (○), Ad5-infected H4 (•), or H4-E1A (▪) cells.

  • FIGURE 2.
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    FIGURE 2.

    Expression of E1A in Ad5-infected compared with E1A-transfected human tumor cells. A2058 cells were infected with Ad5 for 16 h and the levels of E1A oncoprotein expression were determined by Western analysis (see Materials and Methods). A2058-E1A is an E1A-transfected A2058 cell line.

  • FIGURE 3.
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    FIGURE 3.

    Ad5-infection inhibits TRAIL-dependent killing of E1A-transfected cells. Parental and E1A-transfected A2058 cells were mock or Ad5-infected for 16 h and their sensitivity to TRAIL-induced killing was determined in a 16-h cytolysis assay. TRAIL-induced lysis of A2058 (○), Ad5-infected A2058-E1A (•), or uninfected A2058-E1A cells (▪).

  • FIGURE 4.
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    FIGURE 4.

    E1B and E3 gene products inhibit TRAIL-dependent killing. H5dl250 and H5dl327 are Ad5-mutants that delete the E1B-19K and E3 open reading frames, respectively. Tumor cell lines were mock-, H5dl250-, or H5-dl327-infected for 16 h and their sensitivity to TRAIL-induced killing was determined in 16-h cytolysis assays. A, TRAIL-induced killing of A2058 (○), A2058-E1A (•), H5dl327- (▪), or H5d/250-infected (□) A2058 cells. B, TRAIL-induced killing of A2058 (○), H5dl327-infected (▪), or unifected-A2058-E1A cells (•).

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The Journal of Immunology: 165 (8)
The Journal of Immunology
Vol. 165, Issue 8
15 Oct 2000
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Adenovirus E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis-Inducing Ligand (TRAIL)
John M. Routes, Sharon Ryan, Amanda Clase, Tanya Miura, Alicia Kuhl, Terry A. Potter, James L. Cook
The Journal of Immunology October 15, 2000, 165 (8) 4522-4527; DOI: 10.4049/jimmunol.165.8.4522

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Adenovirus E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis-Inducing Ligand (TRAIL)
John M. Routes, Sharon Ryan, Amanda Clase, Tanya Miura, Alicia Kuhl, Terry A. Potter, James L. Cook
The Journal of Immunology October 15, 2000, 165 (8) 4522-4527; DOI: 10.4049/jimmunol.165.8.4522
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