Stebel A, Brachetti C, Kunkel M, Schmidt M, Fritz G
Department of Toxicology, University of Mainz, D-55131 Mainz, Germany.
Oncol Rep. 2009 Jan;21(1):217-22.
In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely related to the plasminogen activator inhibitor (PAI-1) and estrogen receptor (ER) expression but not the progesterone receptor (PR) and urokinase plasminogen activator (uPA). A low Tiam1 expression was associated with p53 positivity without being related to HER2/neu status. The data show that Tiam1 expression decreases with the progression of breast carcinomas and is inversely associated with several established breast tumor markers. Therefore, we suggest that Tiam1 counteracts the progression of breast carcinomas and is suitable as a novel breast tumor marker.
在本研究中，我们通过免疫组织化学方法调查了106例乳腺肿瘤标本中Ras同源（Rho）GTP酶和Rho鸟嘌呤交换因子（GEF）T细胞淋巴瘤侵袭转移因子1（Tiam1）的表达水平。将Rho和Rho-GEF的表达评分与临床确定的诊断和预后参数进行比较。我们发现，RhoA和RhoB评分随肿瘤分级略有增加，而Rac1评分不受影响。Rac1特异性GEF Tiam1的影响最为显著。Tiam1表达评分随肿瘤分级、肿瘤扩散和增殖的增加而显著降低。此外，Tiam1表达与纤溶酶原激活物抑制剂（PAI-1）和雌激素受体（ER）表达呈负相关，但与孕激素受体（PR）和尿激酶型纤溶酶原激活物（uPA）无关。低Tiam1表达与p53阳性相关，而与HER2/neu状态无关。数据表明，Tiam1表达随乳腺癌进展而降低，并与几种已确立的乳腺肿瘤标志物呈负相关。因此，我们认为Tiam1可对抗乳腺癌的进展，适合作为一种新型乳腺肿瘤标志物。
