Identification of XAGE-1 isoforms: predominant expression of XAGE-1b in testis and tumors.
XAGE-1 is a cancer/testis (CT) antigen and has been shown to be immunogenic in lung cancer patients. Among 4 alternative splicing variants, XAGE-1a, b, c and d, XAGE-1b mRNA was dominantly expressed in cancer. In this study, we generated a XAGE-1b mAb, USO9-13. The B cell epitope recognized by the USO9-13 mAb was in the C-terminal region of the XAGE-1b protein and is also recognized by sera from patients with lung adenocarcinoma. Using USO9-13 and an anti-Flag mAb, we examined the translation products of the 4 transcripts. The XAGE-1a and b transcripts translated to the XAGE-1b protein. The XAGE-1c transcript possibly translated to 9- and 17-aa polypeptides. The XAGE-1d transcript translated to a protein consisting of 69 amino acids. Immunofluorescence analysis using USO9-13 mAb showed that the XAGE-1b protein is located in the nuclei of cells. Immunohistochemically, nuclear staining was heterogeneously observed in 25/47 lung adenocarcinomas, 1/12 hepatocellular carcinomas and 1/11 gastric cancers, but not in adjacent normal tissues. These findings suggested that XAGE-1b is a promising target molecule for a cancer vaccine against lung cancer.
Sato
Shuichiro
S
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan. sato-s@md.okayama-u.ac.jp
Noguchi
Yuji
Y
Ohara
Nobuya
N
Uenaka
Akiko
A
Shimono
Michihide
M
Nakagawa
Kazuhiko
K
Koizumi
Fumihito
F
Ishida
Toshiaki
T
Yoshino
Tadashi
T
Shiratori
Yasushi
Y
Nakayama
Eiichi
E
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism; D013737:Testis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D020033:Protein Isoforms; C413656:XAGE1A protein, human