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首页> 外文期刊>Cellular Physiology and Biochemistry >LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro
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LAPTM4B Predicts Axillary Lymph Node Metastasis in Breast Cancer and Promotes Breast Cancer Cell Aggressiveness in Vitro

机译:LAPTM4B预测乳腺癌的腋窝淋巴结转移并促进体外乳腺癌细胞的侵袭性

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>Purpose: Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is associated with the prognosis of several human malignancies. In this study, the role of LAPTM4B in the metastatic potential of breast cancer (BC) and its underlying molecular mechanisms were investigated. Methods: The relationship between LAPTM4B expression and axillary lymph node metastasis was determined in 291 BC specimens by immunohistochemistry. The expression of LAPTM4B in paired BC cells was overexpressed and inhibited to analyse the role of LAPTM4B in the aggressiveness of BC. Cell proliferation, migration and invasion were assessed in vitro. Metastasis-related protein levels were detected through Western blot. Results: Immunohistochemical staining demonstrated that high expression level of LAPTM4B was independently associated with axillary lymph node metastasis (odds ratio=2.428; 95%CI=1.333- 4.425; P=0.004). The LAPTM4B inhibition in MCF-7 cells inhibited cell proliferation, migration, invasion, and resulted in simultaneous downregulation of phosphorylated N-cadherin, vimentin, and upregulation of E-cadherin. By contrast, the LAPTM4B overexpression promoted cell proliferation, migration, invasion, and led to simultaneous upregulation of N-cadherin, vimentin, and downregulation of E-cadherin in T47D cells. Conclusions: High expression level of LAPTM4B predicts tumor metastatic potential in patients with BC. Our results provide the first evidence of the role of LAPTM4B as an Epithelial-mesenchymal transition (EMT) inducer that promotes aggressiveness in BC cells.
机译:> 目的: 溶酶体相关蛋白跨膜4β(LAPTM4B)与几种人类恶性肿瘤的预后相关。在这项研究中,研究了LAPTM4B在乳腺癌(BC)转移潜力中的作用及其潜在的分子机制。 方法: 通过免疫组织化学测定了291 BC样本中LAPTM4B表达与腋窝淋巴结转移之间的关系。 LAPTM4B在成对的BC细胞中的表达被过表达和抑制,以分析LAPTM4B在BC侵袭性中的作用。在体外评估细胞的增殖,迁移和侵袭。通过蛋白质印迹检测与转移相关的蛋白水平。 结果: 免疫组织化学染色显示,LAPTM4B的高表达水平与腋窝淋巴结转移独立相关(赔率= 2.428; 95%CI = 1.333-4.425; P = 0.004)。 MCF-7细胞中的LAPTM4B抑制作用抑制了细胞增殖,迁移,侵袭,并导致磷酸化的N-钙黏着蛋白,波形蛋白和E-钙黏着蛋白的同时下调。相比之下,LAPTM4B的过表达促进细胞增殖,迁移,侵袭,并导致T47D细胞中N-钙黏着蛋白,波形蛋白和E-钙黏着蛋白的同时上调。 结论: LAPTM4B的高表达水平可预测BC患者的肿瘤转移潜力。我们的结果提供了LAPTM4B作为上皮-间质转化(EMT)诱导剂的作用的第一个证据,该诱导剂可促进BC细胞的侵袭性。

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