Chan Victor Y W, Chan Michael W Y, Leung Wai-Keung, Leung Po-Sing, Sung Joseph J Y, Chan Francis K L
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Regul Pept. 2005 Apr 15;127(1-3):87-94. doi: 10.1016/j.regpep.2004.10.016.
Intestinal trefoil factor (TFF3) is essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. We previously showed that TFF3 was overexpressed in gastric carcinoma. Whether TFF3 possesses malignant potential is not fully elucidated. We sought to investigate the effects of inducting TFF3 expression in a non-malignant rat fibroblast cell line (Rat-2) on the cell proliferation, invasion and the genes regulating cell invasion. Invasiveness and proliferation of transfected Rat-2 cell line were assessed using in vitro invasion chamber assay and colorimetric MTS assay. Differential mRNA expressions of invasion-related genes, namely, metalloproteinases (MMP-9), tissue inhibitors of metalloproteinases (TIMP-1), beta-catenin and E-cadherin, were determined by quantitative real-time polymerase chain reaction (PCR). We showed that TFF3 did not inhibit the proliferation of Rat-2 cells. We also demonstrated that transfection of TFF3 significantly promoted invasion of Rat-2 cells by 1.4- to 2.2-folds. There was an upregulation of beta-catenin (13.1-23.0%) and MMP-9 (43.4-92.2%) mRNA expression levels, and downregulation of E-cadherin (25.6-33.8%) and TIMP-1 (31.5-37.8%) in TFF3-transfected cells compared to controls during 48-h incubation. Our results suggested that TFF3 possesses malignant potential through promotion of cell invasiveness and alteration of invasion-related genes.
肠三叶因子（TFF3）在调节细胞迁移和维持胃肠道黏膜完整性方面至关重要。我们之前的研究表明，TFF3在胃癌中过表达。TFF3是否具有恶性潜能尚未完全阐明。我们试图研究在非恶性大鼠成纤维细胞系（Rat-2）中诱导TFF3表达对细胞增殖、侵袭以及调节细胞侵袭的基因的影响。使用体外侵袭小室试验和比色MTS试验评估转染后的Rat-2细胞系的侵袭性和增殖能力。通过定量实时聚合酶链反应（PCR）测定侵袭相关基因，即金属蛋白酶（MMP-9）、金属蛋白酶组织抑制剂（TIMP-1）、β-连环蛋白和E-钙黏蛋白的差异mRNA表达。我们发现TFF3不会抑制Rat-2细胞的增殖。我们还证明，转染TFF3可使Rat-2细胞的侵袭能力显著提高1.4至2.2倍。在48小时孵育期间，与对照组相比，TFF3转染细胞中β-连环蛋白（13.1 - 23.0%）和MMP-9（43.4 - 92.2%）的mRNA表达水平上调，E-钙黏蛋白（25.6 - 33.8%）和TIMP-1（31.5 - 37.8%）下调。我们的结果表明，TFF3通过促进细胞侵袭和改变侵袭相关基因而具有恶性潜能。
