title: Novel spliced form of a lens protein as a novel lung cancer antigen, Lengsin splicing variant 4.
abstract: A glutamine synthetase I family protein, Lengsin, was previously identified as a novel lens-specific transcript in the vertebrate eye. In this report, we show for the first time that Lengsin is a novel tumor-associated antigen expressed ectopically in lung cancer. Interestingly, a novel spliced form of human Lengsin termed 'splicing variant 4', gaining exon 3 that codes extra 63 amino acids, is the dominant transcript form in lung cancer cells. Lengsin mRNA could be detected in 7 of 12 (58%) lung cancer cell lines and 7 of 7 (100%) surgically resected lung cancer tissues. On the other hand, Lengsin transcripts could not be detected in normal major tissues or in other cancer cell lines, including melanoma, colorectal carcinoma, breast carcinoma and hepatocellular carcinoma. In addition, knockdown of Lengsin mRNA with RNAi caused cell death and a decrease of cell viability, suggesting that Lengsin has some essential role in cell survival. Since the lens is an immune-privileged site, we regard Lengsin as a highly immunogenic cancer antigen. Anti-Lengsin autoantibodies were detectable in sera of lung cancer patients, although these patients did not show any lens-related disturbances. Hence, Lengsin splicing variant 4 might be an immunogenic lung cancer-specific antigen that is suitable as a diagnostic marker and for molecular targeting therapy, including immunotherapy.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Akari
authors.initials: A
authors.lastname: Takahashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Inoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Kiriyama
authors.forename: Emiri
authors.initials: E
authors.lastname: Nakazawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Takasu
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kamiguchi
authors.forename: Noriharu
authors.initials: N
authors.lastname: Shijubo
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Honda
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nomura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology; D000368:Aged; D000951:Antigens, Neoplasm; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000276:immunology*; D019154:Protein Splicing; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D005136:Eye Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005974:Glutamate-Ammonia Ligase; C507977:LGSN protein, human