Nuclear β-catenin in basal cell carcinoma correlates with increased proliferation
Nuclear β-catenin in basal cell carcinoma correlates with increased proliferation
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DOI：
10.1111/j.1365-2133.2004.06048.x
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发表时间：
2004-07-01
影响因子：
10.3
通讯作者：
Fletcher, A
中科院分区：
文献类型：
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作者：
Saldanha, G;Ghura, V;Fletcher, A
背景 事实上，所有 BCC 都存在 Hedgehog (Hh) 信号通路失调，并且一部分显示核 β-连环蛋白积聚。后者被认为是由于 Hh 途径定向的 Wnt 表达，但这尚未经过测试。核β-连环蛋白积累的另一个原因是基因突变，它可以稳定蛋白质。理论上，E-钙粘蛋白表达的减少也很重要，因为它可以将 β-连环蛋白隔离在细胞膜上。反过来，核β-catenin可以增加MYC和cyclin D1的表达，从而潜在地改变增殖。目的评估核β-catenin是否出现在BCC中，并探讨潜在的原因和后果。方法通过免疫组织化学评估核β-catenin，并通过E-cadherin表达、β-catenin外显子3突变和WNT5A表达分析其原因。通过分析增殖来评估其后果。结果我们使用免疫组织化学方法在 86 个 BCC 石蜡包埋切片中的 20 个中发现了核 β-连环蛋白。 BCC 显示 WNT5A 相对于周围皮肤有所增加。 10例β-catenin基因外显子3未发现突变。 β-连环蛋白定位和 E-钙粘蛋白表达之间没有关联。具有核β-连环蛋白的肿瘤具有显着更高的增殖能力（P < 0.01）。结论 β-连环蛋白基因突变的缺失表明Hh通路导向的Wnt信号传导仍然是BCC中核β-连环蛋白积累的最可能原因。此外，与增殖增加的相关性是核β-连环蛋白可能具有生物效应的第一个证据。然而，Hh 通路失调与 Wnt 配体过度表达之间存在因果关系。核β-连环蛋白的积累和增殖的增加仍有待证实。
Background Virtually all BCCs have deregulation of the Hedgehog (Hh) signalling pathway and a proportion show nuclear beta-catenin accumulation. The latter is thought to be due to Hh pathway-directed Wnt expression but this has not been tested. An alternative cause of nuclear beta-catenin accumulation is gene mutation, which stabilizes the protein. Theoretically, reduced E-cadherin expression could also be important because it can sequester beta-catenin at the cell membrane. In turn, nuclear beta-catenin can increase expression of MYC and cyclin D1, thus potentially altering proliferation.Objectives To assess whether nuclear beta-catenin occurs in BCC, and to look at potential causes and consequences.Methods Nuclear beta-catenin was assessed by immunohistochemistry, and its causes by analysis of E-cadherin expression, beta-catenin exon 3 mutation and WNT5A expression. Its consequences were assessed by analysing proliferation.Results We found nuclear beta-catenin in 20 of 86 paraffin-embedded sections of BCCs using immunohistochemistry. BCCs showed increased WNT5A relative to the surrounding skin. No mutations in exon 3 of the beta-catenin gene were found in 10 cases. There was no association between beta-catenin localization and E-cadherin expression. Tumours with nuclear beta-catenin had significantly higher proliferation (P < 0.01).Conclusions The absence of beta-catenin gene mutations indicate that the Hh pathway-directed Wnt signalling remains the most likely cause of nuclear beta-catenin accumulation in BCC. Additionally, the correlation with increased proliferation is the first evidence that nuclear beta-catenin may have a biological effect. However, a causal link between Hh pathway deregulation, Wnt ligand overexpression. nuclear beta-catenin accumulation and increased proliferation remains to be confirmed.