Faculty Collaboration Database

Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis-inducing ligand (TRAIL). J Immunol 2000 Oct 15;165(8):4522-7

Date

10/18/2000

Pubmed ID

11035092

DOI

10.4049/jimmunol.165.8.4522

Scopus ID

2-s2.0-0034667997 (requires institutional sign-in at Scopus site)   65 Citations

Abstract

Expression of the adenovirus serotype 5 (Ad5) E1A oncogene sensitizes cells to apoptosis by TNF-alpha and Fas-ligand. Because TNF-related apoptosis-inducing ligand (TRAIL) kills cells in a similar manner as TNF-alpha and Fas ligand, we asked whether E1A expression might sensitize cells to lysis by TRAIL. To test this hypothesis, we examined TRAIL-induced killing of human melanoma (A2058) or fibrosarcoma (H4) cells that expressed E1A following either infection with Ad5 or stable transfection with Ad5-E1A. E1A-transfected A2058 (A2058-E1A) or H4 (H4-E1A) cells were highly sensitive to TRAIL-induced killing, but Ad5-infected cells expressing equally high levels of E1A protein remained resistant to TRAIL. Infection of A2058-E1A cells with Ad5 reduced their sensitivity to TRAIL-dependent killing. Therefore, viral gene products expressed following infection with Ad5 inhibited the sensitivity to TRAIL-induced killing conferred by transfection with E1A. E1B and E3 gene products have been shown to inhibit TNF-alpha- and Fas-dependent killing. The effect of these gene products on TRAIL-dependent killing was examined by using Ad5-mutants that did not express either the E3 (H5dl327) or E1B-19K (H5dl250) coding regions. A2058 cells infected with H5dl327 were susceptible to TRAIL-dependent killing. Furthermore, TRAIL-dependent killing of A2058-E1A cells was not inhibited by infection with H5dl327. Infection with H5dl250 sensitized A2058 cells to TRAIL-induced killing, but considerably less than H5dl327-infection. In summary, expression of Ad5-E1A gene products sensitizes cells to TRAIL-dependent killing, whereas E3 gene products, and to a lesser extent E1B-19K, inhibit this effect.

Author List

Routes JM, Ryan S, Clase A, Miura T, Kuhl A, Potter TA, Cook JL

Author

John M. Routes MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenovirus E1A Proteins
Adenovirus E1B Proteins
Adenovirus E3 Proteins
Adenoviruses, Human
Apoptosis
Apoptosis Regulatory Proteins
Cytotoxicity, Immunologic
Fibrosarcoma
Gene Expression Regulation, Viral
Humans
Ligands
Melanoma
Membrane Glycoproteins
Oncogenes
TNF-Related Apoptosis-Inducing Ligand
Transfection
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha