title: Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer.
abstract: Tob is a member of the Tob/BTG family, a novel class of anti-proliferative proteins. To investigate the involvement of tob as a tumor suppressor gene in human lung cancer, we analyzed the expression of tob mRNA and protein in lung cancer tissue and adjacent normal lung tissue. Immunohistochemical analysis using anti-Tob antibody showed decreased expression of Tob in 72% (31/43) of lung cancer tissues. Furthermore, 95% (19/20) of squamous cell carcinoma patients showed an apparent decrease in Tob in cancer tissues, associated with smoking status. The phosphorylated form of Tob, an inactive form of Tob, was detected in 76% (16/21) of cancer tissues of adenocarcinoma patients, but not in normal alveolar epithelial cells. Either a decrease in Tob expression or an accumulation of phosphorylated Tob was observed from early clinical stages, even in bronchial dysplasia, a premalignant lesion of squamous cell carcinoma. The above findings suggest that the disruption of anti-proliferative Tob plays a distinct part in the early stage of lung carcinogenesis.
authors.affiliation: Department of Internal Medicine, Saga Medical School, Saga 849-8501, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwanaga
authors.forename: Naoko
authors.initials: N
authors.lastname: Sueoka
authors.forename: Akemi
authors.initials: A
authors.lastname: Sato
authors.forename: Toru
authors.initials: T
authors.lastname: Sakuragi
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Sakao
authors.forename: Masaki
authors.initials: M
authors.lastname: Tominaga
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Junko
authors.initials: J
authors.lastname: K-Tsuzuku
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hayashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Eisaburo
authors.initials: E
authors.lastname: Sueoka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D001980:Bronchi / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
chemical_list: D002352:Carrier Proteins; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins