Nuclear accumulation of β-catenin in human endocrine tumors:: Association with Ki-67 (MIB-1) proliferative activity
Nuclear accumulation of β-catenin in human endocrine tumors:: Association with Ki-67 (MIB-1) proliferative activity
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DOI：
10.1385/ep:11:3:243
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Sasano, H
中科院分区：
文献类型：
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作者：
Semba, S;Kusumi, R;Sasano, H
β-连环蛋白与肿瘤的侵袭、转移和预后密切相关。最近的研究表明，β-连环蛋白的异常表达，尤其是其核积聚，在无翼/Wnt信号通路中也起着重要作用。本研究应用免疫组织化学方法检测了93例人类内分泌相关肿瘤中β-连环蛋白的核定位，包括1例髓样癌(甲状腺)、12例甲状旁腺肿瘤、22例类癌(消化道和肝脏)、7例胰岛细胞瘤、26例肾上腺皮质肿瘤、13例神经母细胞瘤(肾上腺)和12例嗜铬细胞瘤(肾上腺)，并研究了β-连环蛋白基因的遗传变化。在22例类癌中8例(36%)和7例胰岛细胞瘤中2例(29%)检测到β-连环蛋白的核聚集。经GSK-3β磷酸化的富含丝氨酸/苏氨酸结构域的β-连环蛋白基因外显子3在任何一组内分泌肿瘤中均未检测到遗传改变。然而，在类癌中，β-连环蛋白的核积聚与增殖标记物Ki-67(MiB-1)标记指数显著相关(p<；0.001)。我们的发现表明，核转移和-连环蛋白的积聚可能作为一种癌蛋白在类癌肿瘤的发生中起作用。
beta -Catenin is closely associated with carcinoma invasion/metastasis and poor survival. Recent studies have demonstrated that abnormal expression of beta -catenin, especially its nuclear accumulation, also plays an important role in wingless/Wnt signaling pathway In this study, we evaluated immunohistochemically the nuclear localization of beta -catenin in a total of 93 human-endocrine-related tumors including 1 medullary carcinoma (thyroid gland), 12 parathyroid tumors, 22 carcinoid tumors (digestive tract and liver), 7 islet cell tumors, 26 adrenocortical tumors, 13 neuroblastoma (adrenal gland), and 12 pheochromocytoma (adrenal gland), and also studied genetic alterations of the beta -catenin gene. Nuclear accumulation of beta -catenin was frequently detected in 8 of 22 (36%) carcinoid tumors and 2 of 7 (29%) islet cell tumors. No genetic alteration in exon 3 of the beta -catenin gene encoding serine/threonine rich domain, which was phosphorylated by GSK-3 beta, was detected in any groups of the endocrine tumors. However, nuclear accumulation of beta -catenin in carcinoid tumors was significantly correlated with the proliferative marker Ki-67 (MIB-1) labeling index (p < 0.001). Our findings suggest that nuclear transfer and accumulation of the -catenin may contribute in the tumorigenesis of carcinoid tumor as an oncoprotein.