Metastasis and Angiogenesis Research Group, Department of Surgery, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
Int J Mol Med. 2010 Nov;26(5):723-34. doi: 10.3892/ijmm_00000519.
Occludin is an integral membrane protein localised at tight junctions (TJs). It has become clear that the TJ is an important structure that cancer cells must overcome in order to metastasize successfully. The purpose of this study was to elucidate the importance of the expression of occludin in human breast cancer. Human tissues and breast cancer cell lines were amplified for functional regions of occludin. Tumour tissues showed truncated and/or variant signals. There was also considerable variation in the expression of occludin in the 10 human breast cancer cell lines investigated. Western blotting demonstrated that variants in the MDA-MB-231 and MCF-7 human breast cancer cell lines did not fit the expected occludin signals for changes in phosphorylation status. Immunostaining showed similarly disparate levels of expression. Ribozyme knockdown resulted in increased invasion, reduced adhesion and significantly reduced TJ functions. Q-RT-PCR analysis of 124 tumour and 33 background human breast tissues showed occludin to be significantly decreased in patients with metastatic disease. Immunohistochemical staining showed a decreased expression of occludin in the tumour sections. This study demonstrates for the first time that occludin is differentially expressed in human breast tumour tissues and cell lines. This loss of or aberrant expression has clear repercussions as to the importance of occludin in maintaining TJ integrity in breast tissues. Such inappropriate expression could play a part in breast cancer development.
紧密连接相关蛋白 4（occludin）是一种定位于紧密连接（TJs）的完整膜蛋白。目前已经明确，TJ 是癌细胞成功转移必须克服的重要结构。本研究旨在阐明 occludin 在人乳腺癌中的表达的重要性。扩增了人组织和乳腺癌细胞系的 occludin 功能区域。肿瘤组织显示截短和/或变异信号。在所研究的 10 个人乳腺癌细胞系中，occludin 的表达也存在很大差异。Western blot 表明 MDA-MB-231 和 MCF-7 人乳腺癌细胞系中的变体不符合磷酸化状态变化的预期 occludin 信号。免疫染色显示类似的表达水平差异。核酶敲低导致侵袭增加、粘附减少和 TJ 功能显著降低。对 124 例肿瘤和 33 例背景人乳腺组织的 Q-RT-PCR 分析显示，转移性疾病患者的 occludin 显著降低。免疫组织化学染色显示肿瘤组织中 occludin 的表达减少。本研究首次证明，occludin 在人乳腺癌组织和细胞系中存在差异表达。这种缺失或异常表达对 occludin 在维持乳腺组织 TJ 完整性中的重要性有明显的影响。这种不适当的表达可能在乳腺癌的发展中起作用。
