Bukholm I K, Nesland J M, Kåresen R, Jacobsen U, Børresen-Dale A L
Department of Genetics, Norwegian Radium Hospital, Oslo, Norway.
J Pathol. 1998 Jul;185(3):262-6. doi: 10.1002/(SICI)1096-9896(199807)185:3<262::AID-PATH97>3.0.CO;2-Y.
In the metastatic process, various cell-cell adhesion molecules seem to play an important role. E-cadherin, a transmembrane protein with an extracellular and an intracellular domain, is one of the key players involved in cell-cell adhesion. The function of E-cadherin in preventing metastasis in tumour development is believed to be dependent on intracellular catenins. In a previous study, the expression of E-cadherin was examined in a series of human breast carcinomas. In that study, down-regulation of E-cadherin failed to correlate with lymph node and/or distant metastasis. In the present study, the expression of alpha-, beta-, and gamma-catenins has been examined in a subset of the same tumours in order to evaluate their possible role in breast cancer metastasis. Tumour tissues from 90 primary breast carcinomas were immunostained for alpha-, beta-, and gamma-catenins. Reduced or absent immunoreactivity in the tumour tissue was seen in 63 (70.0 per cent) for alpha-catenin, in 50 (55.6 per cent) for beta-catenin, and in 50 (55.6 per cent) for gamma-catenin. Reduced expression of each of the catenins alone failed to correlate to metastasis. However, when all of the four proteins (E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin) were analysed as one group, a significant association was seen between reduction in immunoreactivity of at least one of these four proteins and the presence of metastases. These results indicate that if one of these proteins is down-regulated, the function of the others in suppressing metastasis is altered. A significant association was seen between lobular invasive tumours and beta-catenin expression.
在转移过程中，各种细胞间粘附分子似乎起着重要作用。E-钙粘蛋白是一种具有细胞外和细胞内结构域的跨膜蛋白，是参与细胞间粘附的关键分子之一。E-钙粘蛋白在肿瘤发生过程中预防转移的功能被认为依赖于细胞内连环蛋白。在先前的一项研究中，对一系列人类乳腺癌中E-钙粘蛋白的表达进行了检测。在该研究中，E-钙粘蛋白的下调与淋巴结转移和/或远处转移无关。在本研究中，为了评估α-、β-和γ-连环蛋白在乳腺癌转移中的可能作用，对同一组肿瘤中的一部分进行了检测。对90例原发性乳腺癌的肿瘤组织进行了α-、β-和γ-连环蛋白的免疫染色。在肿瘤组织中，α-连环蛋白免疫反应性降低或缺失的有63例（70.0%），β-连环蛋白有50例（55.6%），γ-连环蛋白有50例（55.6%）。单独每种连环蛋白表达降低均与转移无关。然而，当将这四种蛋白（E-钙粘蛋白、α-连环蛋白、β-连环蛋白和γ-连环蛋白）作为一组进行分析时，发现这四种蛋白中至少一种免疫反应性降低与转移的存在之间存在显著关联。这些结果表明，如果其中一种蛋白下调，其他蛋白在抑制转移中的功能就会改变。小叶浸润性肿瘤与β-连环蛋白表达之间存在显著关联。
