Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer

Alteration of expression or phosphorylation status of tob, a novel tumor suppressor gene product, is an early event in lung cancer
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DOI:
10.1016/j.canlet.2003.08.019
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发表时间:
2003-12-08
期刊:
影响因子:
9.7
通讯作者:
Sueoka, E
Sueoka, E
中科院分区:
医学1区
文献类型:
--
作者:
Iwanaga, K;Sueoka, N;Sueoka, E

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Tob是Tob/BTG家族的成员,Tob/BTG家族是一类新的抗增殖蛋白。为了探讨tob作为抑癌基因在肺癌中的作用,我们检测了tob基因在肺癌组织和癌旁正常肺组织中的表达。抗Tob抗体免疫组化显示72%(31/43)的肺癌组织中Tob表达降低。此外,95%(19/20)的鳞状细胞癌患者癌组织中Tob明显降低,与吸烟状态相关。磷酸化形式的Tob,一种非活性形式的Tob,检测到腺癌患者的癌组织中的76%(16/21),而不是在正常肺泡上皮细胞。从早期临床阶段观察到Tob表达减少或磷酸化Tob积累,即使在支气管发育不良(鳞状细胞癌的癌前病变)中也是如此。上述结果表明,抗增殖Tob的破坏在肺癌发生的早期阶段起着独特的作用。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
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 antiproliferative Tob plays a distinct part in the early stage of lung carcinogenesis. (C) 2003 Elsevier Ireland Ltd. All rights reserved.