核 Kaiso 表达与高级别和三阴性浸润性乳腺癌有关。,PLOS ONE

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核 Kaiso 表达与高级别和三阴性浸润性乳腺癌有关。
PLOS ONE ( IF 2.9 ) Pub Date : 2012-05-25 , DOI: 10.1371/journal.pone.0037864
Jeroen F Vermeulen ₁ , Robert A H van de Ven , Cigdem Ercan , Petra van der Groep , Elsken van der Wall , Peter Bult , Matthias Christgen , Ulrich Lehmann , Juliet Daniel , Paul J van Diest , Patrick W B Derksen

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Kaiso 是一种 BTB/POZ 转录因子，在多种细胞类型中普遍表达，并作为转录抑制因子和激活因子发挥作用。关于 Kaiso 在乳腺癌中的表达和定位知之甚少。在这里，我们获得了与 477 例人类浸润性乳腺癌中 Kaiso 表达相关的病理特征和分子亚型。核 Kaiso 主要见于浸润性导管癌 (IDC) (p = 0.007)，而细胞质 Kaiso 表达与浸润性小叶癌 (ILC) (p = 0.006) 相关。尽管细胞质 Kaiso 与临床病理特征无关，但我们发现核 Kaiso、高组织学分级 (p = 0.023)、ERα 阴性 (p = 0.001) 与 HER2 驱动和基底/三阴性乳腺癌之间存在显着相关性。 p = 0.018）。有趣的是，核 Kaiso 在 BRCA1 相关的乳腺癌（p<0.001）和过度表达 EGFR 的浸润性乳腺癌（p = 0.019）中也很丰富。我们观察到核 Kaiso 与膜定位 E-钙粘蛋白和 p120-连环蛋白 (p120) 之间的相关性 (p<0.01)。相比之下，细胞质 p120 与 E-钙粘蛋白的丧失和低核 Kaiso 密切相关（p = 0.005）。我们可以在人 ILC 细胞和源自 ILC 条件小鼠模型的细胞系中证实这些发现。此外，我们提供的功能数据证实了一种机制，即 E-钙粘蛋白控制 p120 介导的 Kaiso 依赖性基因抑制的缓解。总之，我们的数据表明核Kaiso在临床侵袭性导管乳腺癌中很常见，而细胞质Kaiso和p120介导的Kaiso依赖性转录抑制的缓解是ILC的特征。

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Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC) (p = 0.007), while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC) (p = 0.006). Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023), ERα negativity (p = 0.001), and the HER2-driven and basal/triple-negative breast cancers (p = 0.018). Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001) and invasive breast cancer overexpressing EGFR (p = 0.019). We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120) (p<0.01). In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005). We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

更新日期：2019-11-01

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