Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer.
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.
Iwanaga
Kentaro
K
Department of Internal Medicine, Saga Medical School, Saga 849-8501, Japan.
Sueoka
Naoko
N
Sato
Akemi
A
Sakuragi
Toru
T
Sakao
Yukinori
Y
Tominaga
Masaki
M
Suzuki
Toru
T
Yoshida
Yutaka
Y
K-Tsuzuku
Junko
J
Yamamoto
Tadashi
T
Hayashi
Shinichiro
S
Nagasawa
Kohei
K
Sueoka
Eisaburo
E
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
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