Nuclear Snail1 and nuclear ZEB1 protein expression in invasive and intraductal human breast carcinomas.
Nuclear Snail1 and nuclear ZEB1 protein expression in invasive and intraductal human breast carcinomas.
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DOI：
10.1016/j.humpath.2010.11.004
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发表时间：
2011-08
期刊：
影响因子：
3.3
通讯作者：
Bachelder RE
中科院分区：
文献类型：
--
作者：
Geradts J;de Herreros AG;Su Z;Burchette J;Broadwater G;Bachelder RE
Snail1 和 ZEB1 是转录抑制因子，可在动物模型中驱动肿瘤的发生和转移。 Snail1 和 ZEB1 经常在肿瘤细胞系中共表达，表明这些因子可能协同促进肿瘤进展。然而，这些转录抑制因子在原发性人类癌症标本中的共表达尚未得到研究。先前的研究评估了 Snail1 信使 RNA 在原发性乳腺癌中的表达，这并不反映 Snail1 的活性，因为 Snail1 会受到抑制其核定位/活性的翻译后修饰。在当前的研究中，使用已知Snail1和ZEB1表达状态的乳腺肿瘤细胞系，我们开发了用于检测核Snail1和核ZEB1蛋白的免疫组织化学方案。使用这些方案，我们评估了不同亚型的原发性人类乳腺癌中的核 Snail1 和核 ZEB1 表达 (n = 78)。核Snail1和雌激素受体α表达在原发性乳腺癌中呈负相关，核Snail1在大约80%的三阴性乳腺癌中表达（缺乏雌激素受体α、孕激素受体和人表皮生长因子受体2过表达）。相比之下，核ZEB1在这些乳腺癌中的表达频率明显较低。值得注意的是，在 45% 的导管原位癌标本中检测到核 Snail1 蛋白（n = 29），这提出了早期乳腺病变中核 Snail1 表达可能预测浸润性乳腺癌未来发展的重要可能性。总的来说，我们的研究表明，在侵袭性三阴性乳腺癌以及导管内癌中，核 Snail1 频繁表达，但核 ZEB1 不表达。
Snail1 and ZEB1 are transcriptional repressors that drive tumor initiation and metastasis in animal models. Snail1 and ZEB1 are frequently coexpressed in tumor cell lines, suggesting that these factors may cooperate to promote tumor progression. However, coexpression of these transcriptional repressors in primary human cancer specimens has not been investigated. Previous studies assessed expression in primary breast cancers of Snail1 messenger RNA, which does not reflect Snail1 activity because Snail1 is subject to posttranslational modifications that inhibit its nuclear localization/activity. In the current study, using breast tumor cell lines of known Snail1 and ZEB1 expression status, we developed immunohistochemistry protocols for detecting nuclear Snail1 and nuclear ZEB1 proteins. Using these protocols, we assessed nuclear Snail1 and nuclear ZEB1 expressions in primary human breast cancers of varying subtypes (n = 78). Nuclear Snail1 and estrogen receptor α expression were inversely associated in primary breast cancers, and nuclear Snail1 was expressed in approximately 80% of triple-negative breast cancers (lacking estrogen receptor α, progesterone receptor, and human epidermal growth factor receptor 2 overexpression). In contrast, nuclear ZEB1 was expressed at a significantly lower frequency in these breast cancers. Notably, nuclear Snail1 protein was detected in 45% of ductal carcinoma in situ specimens (n = 29), raising the important possibility that nuclear Snail1 expression in early stage breast lesions may predict future development of invasive breast cancer. Collectively, our studies demonstrate frequent expression of nuclear Snail1, but not nuclear ZEB1, in invasive, triple-negative breast cancers as well as in intraductal carcinomas.