Expression of potential β-catenin targets, cyclin D1, c-Jun, c-Myc, E-cadherin, and EGFR in chemically induced hepatocellular neoplasms from B6C3F1 mice
Expression of potential β-catenin targets, cyclin D1, c-Jun, c-Myc, E-cadherin, and EGFR in chemically induced hepatocellular neoplasms from B6C3F1 mice
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DOI：
10.1016/s0041-008x(03)00170-4
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发表时间：
2003-07-15
影响因子：
3.8
通讯作者：
Devereux, TR
中科院分区：
文献类型：
--
作者：
Anna, CH;Iida, M;Devereux, TR
在这项研究中，我们使用了几种化学致癌物诱导的肝肿瘤，以研究与β-catenin/Wnt信号传导相关的潜在核靶点和潜在的膜相关β-catenin结合伴侣。Western分析发现，无论治疗与否，所有5例肝母细胞瘤均存在细胞周期蛋白D1的强表达，其模式与之前观察到的β-连环蛋白相似。35例肝细胞肿瘤中有12例（34%）细胞周期蛋白D1表达增加。15例Catnb基因突变的肿瘤中有10例（67%）细胞周期蛋白D1表达上调，而20例无Catnb突变的肿瘤中只有2例（10%）细胞周期蛋白D1表达增加。免疫组化分析证实，在大多数肝母细胞瘤细胞核和散在的细胞核染色，有Catnb突变的肝细胞肿瘤细胞周期蛋白D1的强表达。30例肝细胞肿瘤和所有肝母细胞瘤中有19例（63%）观察到c-Jun表达增加，尽管上调与Catnb突变不完全相关。C-Myc表达在肿瘤中没有增加。在一些肿瘤中观察到与β-连环蛋白在膜上相互作用的E-钙粘蛋白的表达减少，但这与Catnb突变无关。表皮生长因子受体的表达可能在β-连环蛋白酪氨酸磷酸化中起作用，在一些肿瘤中的表达低于正常组织，这取决于化学治疗。结果提供的证据表明，细胞周期蛋白D1和c-Jun的表达增加可能会在肿瘤进展过程中提供一个优势，并在从肝细胞肿瘤肝母细胞瘤的过渡。此外，细胞周期蛋白D1表达的增加可能至少部分是由Catnb突变、β-连环蛋白积累和Wnt信号传导增加引起的。(C)2003 Elsevier Science（美国）。All rights reserved.
In this study we used liver neoplasms induced by several chemical carcinogens to investigate potential nuclear targets associated with beta-catenin/Wnt signaling and potential membrane-associated beta-catenin binding partners. Strong expression of cyclin D1, in a pattern similar to that observed previously for beta-catenin, was observed by Western analysis for all five hepatoblastomas examined regardless of treatment. Increased expression of cyclin D1 was also detected in 12 of 35 (34%) hepatocellular neoplasms. Ten of 15 tumors (67%) that had mutations in the Catnb gene had upregulation of cyclin D1, while only 2 of 20 tumors (10%) without Catnb mutations had increased cyclin D1 expression. Immunohistochemical analysis confirmed strong expression of cyclin D1 in most nuclei of hepatoblastomas and scattered nuclear staining in hepatocellular tumors that had Catnb mutations. Increased c-Jun expression was observed in 19 of 30 (63%) hepatocellular tumors and all hepatoblastomas, although upregulation was not completely correlated with Catnb mutation. C-Myc expression was not increased in the tumors. Reduced expression of E-cadherin, which interacts with beta-catenin at the membrane, was observed in some tumors, but this did not correlate with Catnb mutation, Expression of the epidermal growth factor receptor, which may have a role in beta-catenin tyrosine phosphorylation, was lower in some tumors than in normal tissue depending on chemical treatment. The results provide evidence that increased expression of cyclin D1 and c-Jun may provide an advantage during tumor progression and in the transition from hepatocellular neoplasms to hepatoblastomas. Moreover, it is likely increased cyclin D1 expression results at least in part from Catnb mutation, beta-catenin accumulation, and increased Wnt signaling. (C) 2003 Elsevier Science (USA). All rights reserved.