Abnormally high expression of proteasome activator-γ in thyroid neoplasm
Abnormally high expression of proteasome activator-γ in thyroid neoplasm
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DOI：
10.1210/jc.2002-021413
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发表时间：
2003-03-01
影响因子：
5.8
通讯作者：
Shigemasa, C
中科院分区：
文献类型：
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作者：
Okamura, T;Taniguchi, SI;Shigemasa, C
PA 28-γ是20 S蛋白酶体的激活剂，20 S蛋白酶体是在各种细胞类型的细胞周期进程中起重要作用的ATP依赖性蛋白水解系统。在本文中，我们发现PA 28-γ在各种甲状腺肿瘤中的异常高表达。甲状腺样本取自甲状腺正常（4例）和以下疾病患者：乳头状腺癌（13例），多结节性甲状腺肿（4例）和未分化癌（1例）。通过免疫组织化学染色和蛋白质印迹法估计PA 28-γ表达。在所有乳头状腺癌样品中，PA 28-γ异常过表达，特别是在存在于癌块周围区域的癌细胞中或在侵入癌块周围的包膜区域的癌细胞中。在这些区域的癌细胞中，PA 28-γ主要分布在癌细胞的细胞核中而不是细胞质中。另一方面，在邻近的正常甲状腺滤泡细胞中未观察到明显的PA 28-γ表达。在结节性甲状腺肿中，PA 28-γ的表达相对较低，与乳头状腺癌相比。在未分化癌中，PA 28-γ表达水平最高，尤其是在分化差的区域，如未分化癌组织的鳞状化生。因此，PA 28-γ的表达似乎仅限于甲状腺癌细胞，特别是在癌细胞生长速度加快的区域。这一结果进一步得到以下事实的证实：C2、20 S蛋白酶体α亚基和增殖细胞核抗原在该区域中类似地过表达。因此，PA 28-γ可能参与细胞周期的调节系统。此外，甲状腺癌细胞系的生长受到蛋白酶体抑制剂，裂乳胞素β-内酯的影响。这些结果表明，PA 28-γ在甲状腺癌中过表达，特别是在其生长加速细胞中。
PA28-gamma is the activator of 20S proteasome, the ATP-dependent proteolytic system that plays an important role in cell cycle progression in various cell types. In this paper, we show the abnormally high expression of PA28-gamma in various thyroid neoplasms. Thyroid samples were obtained from patients with normal thyroid (4 cases) and with the following diseases: papillary adenocarcinoma (13 cases), multinodular goiter (4 cases), and anaplastic carcinoma (1 case). PA28-gamma expression was estimated by immunohistochemical staining and Western blotting. In all of the papillary adenocarcinoma samples, PA28-gamma was abnormally overexpressed, especially in cancer cells existing at the peripheral region of the cancer mass or in cancer cells invading the capsular region surrounding the cancer mass. In cancer cells of these areas, PA28-gamma was predominantly distributed in nucleus rather than in the cytoplasm of cancer cells. On the other hand, no obvious PA28-gamma expression was observed in the adjacent normal thyroid follicular cells. In multinodular goiter, the expression of PA28-gamma was relatively low compared with papillary adenocarcinoma. In anaplastic carcinoma, PA28-gamma was expressed at the highest level, especially in poorly differentiated regions such as squamous metaplasia of anaplastic cancer tissue. Therefore, the PA28-gamma expression seems to be restricted to thyroid cancer cells, especially in the region where the growth rate of cancer cells is accelerated. This result is further confirmed by the fact that C2, alpha-subunit of 20S proteasome, and proliferating cell nuclear antigen are similarly overexpressed in this region. Thus, PA28-gamma might be involved in the regulatory system for the cell cycle. Moreover, the growth of thyroid cancer cell lines was affected by the proteasome inhibitor, clasto-lactacystin beta-lactone. These results demonstrate that PA28-gamma is overexpressed in thyroid cancer, especially in its growth-accelerated cells.