Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection. J Exp Med 2005 Dec 05;202(11):1477-82
Date
11/30/2005Pubmed ID
16314433Pubmed Central ID
PMC2213342DOI
10.1084/jem.20050240Scopus ID
2-s2.0-28544436492 (requires institutional sign-in at Scopus site) 66 CitationsAbstract
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-Deltap300). Ad5-E1A, but not E1A-Deltap300, 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.
Author List
Routes JM, Ryan S, Morris K, Takaki R, Cerwenka A, Lanier LLMESH terms used to index this publication - Major topics in bold
AdenoviridaeAdenovirus E1A Proteins
Animals
Antineoplastic Agents
Cell Line, Tumor
E1A-Associated p300 Protein
Fibrosarcoma
Genetic Vectors
Graft Rejection
Humans
Kidney
Killer Cells, Natural
Mice
NK Cell Lectin-Like Receptor Subfamily K
Neoplasm Transplantation
Neoplasms, Experimental
Promoter Regions, Genetic
Receptors, Immunologic
Receptors, Natural Killer Cell
Tretinoin
Up-Regulation
