Araujo Thaise G, Marangoni Karina, Rocha Rafael M, Maia Yara C P, Araujo Galber R, Alcântar Tânia M, Alves Patrícia T, Calábria Luanda, Neves Adriana F, Soares Fernando A, Goulart Luiz R
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, MG, Brazil.
Acta Histochem. 2014 Sep;116(7):1178-84. doi: 10.1016/j.acthis.2014.06.008. Epub 2014 Jul 12.
Cytokeratins (CKs) constitute the cytoskeletal network and are regulated by post-translational modifications, acting not only as a mechanical support, but also in cell signaling and regulatory processes. Signaling is mediated by CK-associated proteins, such as Annexin A1 (ANXA1), a ligand of the CK18/CK8 complex. ANXA1 has a pivotal role in cellular and immunological responses, and together with CK18 have been implicated in several processes related to malignant transformation in breast cancer (BC). Our aim was to demonstrate how their interaction might be linked to BC development. We investigated transcript levels, protein expression and distribution for both targets in breast tissues of 92 patients (42 BCs and 50 benign diseases) using qPCR and immunohistochemistry, respectively. ANXA1 and CK18 mRNAs were inversely correlated, and their ratio in each TNM stage significantly differentiated BC from benign diseases (OR=5.62). These differences did not mirror tissue protein levels, but a significant dichotomous protein distribution in tumor tissues was observed, differing from the expected co-localization observed during cell homeostasis. The disequilibrium of transcriptional levels between ANXA1/CK18 and alterations in their tissue distribution are present either in initial events or tumor progression, which suggest a critical event in BC. The broken dialog between ANXA1 and CK18 in normal breast tissues may play a critical role in BC development, and together may be used as combined targets for BC diagnostics.
细胞角蛋白（CKs）构成细胞骨架网络，并受翻译后修饰调控，不仅起到机械支撑作用，还参与细胞信号传导和调节过程。信号传导由与CK相关的蛋白质介导，如膜联蛋白A1（ANXA1），它是CK18/CK8复合物的配体。ANXA1在细胞和免疫反应中起关键作用，并且与CK18一起参与了乳腺癌（BC）中与恶性转化相关的多个过程。我们的目的是证明它们之间的相互作用如何与BC的发展相关联。我们分别使用qPCR和免疫组织化学方法，研究了92例患者（42例BC患者和50例良性疾病患者）乳腺组织中这两个靶点的转录水平、蛋白质表达和分布情况。ANXA1和CK18的mRNA呈负相关，并且它们在每个TNM分期中的比例能够显著区分BC与良性疾病（OR=5.62）。这些差异并未反映组织蛋白水平，但在肿瘤组织中观察到了明显的二分法蛋白质分布，这与细胞稳态期间预期的共定位情况不同。ANXA1/CK18转录水平的失衡及其组织分布的改变在BC的初始事件或肿瘤进展过程中均存在，这表明其在BC中是一个关键事件。正常乳腺组织中ANXA1和CK18之间的对话中断可能在BC发展中起关键作用，并且二者共同可用作BC诊断的联合靶点。
