Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid

Phosphorylation and inactivation of Tob contributes to the progression of papillary carcinoma of the thyroid
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DOI:
10.1016/j.canlet.2004.08.017
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发表时间:
2005-04-08
期刊:
影响因子:
9.7
通讯作者:
Miyauchi, A
Miyauchi, A
中科院分区:
医学1区
文献类型:
--
作者:
Ito, Y;Suzuki, T;Miyauchi, A

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Tob是Tob/BTG家族的成员,是一种新型的抗增殖蛋白,但当磷酸化时变得无活性。在这项研究中,我们研究了Tob是否在各种甲状腺肿瘤中磷酸化和失活,以阐明该事件如何在其进展中发挥作用。Tob磷酸化仅偶尔见于正常滤泡细胞。42.1%的滤泡性腺瘤和14.3%的滤泡性癌中Tob蛋白磷酸化水平较高。乳头状癌中Tob磷酸化水平高于滤泡状癌,39.7%的标本属于高磷酸化组。甲状腺乳头状癌组织中Tob磷酸化水平与肿瘤大小、淋巴结转移、甲状腺外浸润及低分化程度有直接关系。在未分化癌中,令人惊讶的是,在任何情况下都没有观察到Tob磷酸化,但在所有这些情况下也观察到Tob表达的缺陷。这些结果表明:(1)Tob磷酸化通过取消其抗增殖功能而促进乳头状癌的进展,特别是在晚期;(2)未分化癌中Tob表达的缺陷可归因于Tob磷酸化的缺乏。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
Tob, a member of the Tob/BTG family, is a novel anti-proliferative protein, but it becomes inactive when phosphorylated. In this study, we investigated whether Tob is phosphorylated and inactive in various thyroid neoplasms in order to elucidate how this event plays a role in their progression. Tob phosphorylation was only occasionally seen in normal follicular cells. A high level of Tob phosphorylation was observed in 42.1% of follicular adenoma, 14.3% of follicular carcinoma. In papillary carcinoma, the Tob phosphorylation level was elevated more frequently than that in follicular carcinoma, and 39.7% of specimens were classified in the high group. Tob phosphorylation level in papillary carcinoma was directly linked to tumor size, lymph node metastasis, extrathroid extension and the presence of poorly differentiated lesion. In anaplastic carcinoma, surprisingly, Tob phosphorylation was not observed in any cases, but the deficiency of Tob expression was also observed in all these cases. These results suggest that (1) Tob phosphorylation contributes to the progression of papillary carcinoma especially in the later phase through cancellation of its anti-proliferative function, and (2) the deficiency of Tob expression is attributable to the lack of Tob phosphorylation in anaplastic carcinoma. (c) 2004 Elsevier Ireland Ltd. All rights reserved.