title: Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region.
abstract: Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a tumor-promoting factor of largely unknown function. To assess a causative role of EBAG9 in advanced malignancies, we generated the EG7-OVA and MethA murine tumor cell lines that stably express full-length or truncated EBAG9 protein, using retroviral-mediated gene transduction. Upon subcutaneous inoculation into immunocompetent mice, both cell lines showed marked acceleration of in vivo tumor growth when full-length EBAG9 was overexpressed. Interestingly, deletion of the coiled-coil region, thereby producing truncated EBAG9 protein, abolished the tumor-acceleration effect, establishing the importance of this domain in EBAG9-mediated tumor promotion. However, there was no alteration in in vitro cell proliferation or expression levels of MHC class I and co-stimulatory molecules believed to play a role in immune evasion of tumor cells in these tumor cell lines expressing full-length or truncated EBAG9 protein. Furthermore, both full-length and truncated EBAG9 proteins showed a predominantly cytoplasmic localization in the tumor cells. Collectively, these results suggest that EBAG9 overexpression can be causative in enhancing the malignant properties of tumor cells, and that tumor promotion likely requires EBAG9 intracellular association with as yet unidentified binding partners via the coiled-coil region.
authors.affiliation: Group of Human Gene Therapy, Hokkaido University Graduate School of Medicine, N15W7 Sapporo, Hokkaido 060-8638, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maeyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.forename: Shuji
authors.initials: S
authors.lastname: Kubo
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamano
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Iimura
authors.forename: Masafumi
authors.initials: M
authors.lastname: Onodera
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sakiyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen; D002273:Carcinogens / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000235:genetics; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006183:H-2 Antigens / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D012190:Retroviridae / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D002273:Carcinogens; C498919:Cd274 protein, mouse; D017077:Culture Media, Conditioned; C120762:EBAG9 protein, human; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D010455:Peptides; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475824:Vtcn1 protein, mouse; D010047:Ovalbumin