Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues

AIM： To study the molecular forms of trefoil factor 1 （TFF1） in normal gastric mucosa and its expression in normal and abnormal gastric tissues （gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa） and the role of TFF1 in the carcinogenesis and progression of gastric carcinoma and its molecular biological mechanism underlying gastric mucosa protection. METHODS： The molecular forms of TFF1 in normal gastric mucosa were observed by Western blot. The expression of TFF1 in normal and abnormal gastric tissues （gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa） was also assayed by immunohistochemical method. The average positive AO was estimated by Motic Images Advanced 3.0 software. RESULTS： Three patterns of TFF1 were found in normal gastric mucosa： monomer, dimmer, and TFF1 compound whose molecular weight is about 21 kDa. The concentration of TFF1 compound was the highest among these three patterns. TFF1 was expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum, especially around the nuclei. The closer the TFF1 to the lumen, the higher the expression of TFF1, The expression of TFF1 in peripheral tissue of gastric carcinoma （0.51 ± 0.07） was higher than that in normal gastric mucosa （0.44 ± 0.06, P 〈 0.001）. The expression of TFF1 in gastric adenocarcinoma was positively related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma was, the weaker the expression of TFF1. No TFF1 was expressed in poorlydifferentiated adenocarcinoma. The expression of TFF1 in moderately-well differentiated adenocarcinoma （0.45 ± 0.07） was a little lower than that in normal mucosa （P 〉 0.05）. The expression of TFF1 in gastric mucosa with atypical hyperplasia （0.57 ± 0.03） was significantly higher than that in normal gastric mucosa （P 〈 0.001）. No TFF1 was expressed in intestinalized gastric mucosa. There was no statistically significant difference between the expressions of TFFI in gastric mucosa around the intestinalized tissue （0.45 ± 0.07） and normal gastric mucosa （P 〉 0.05）. CONCLUSION： TFF1 is expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum. Its main pattern is TFF1 compound, which may have a greater biological activity than monomer and dimer. The expression of TFF1 in peripheral mucosa of gastric ulcer is higher than that in mucosa 5 cm beyond the ulcer, indicating that TFF1 plays an important part in protection and restitution of gastric mucosa. The expression of TFF1 is increased in peripheral tissues of gastric carcinoma and gastric mucosa with atypical hyperplasia, but is decreased in cancer tissues, implying that TFF1 may be related to suppression and differentiation of carcinoma. The weaker expression of TFF1 in poorly-differentiated carcinoma may be related to the destruction of glands and cells in cancer tissues and the decrease in secretion of TFF1.

胃泌素及其受体拮抗剂对人胃癌细胞株MKN45增殖及TFF1、TFF3表达的影响

目的 探讨17肽胃泌素(Gas-17)及其受体拮抗剂对人胃癌细胞株MKN45增殖及三叶因子1(TTF1)、三叶因子3(TFF3)表达的影响,并分析TTF1、TFF3在胃癌病变过程中的作用。方法培养人胃癌细胞株MKN45后按药物干预分组:第1组:17肽胃泌素组,培养液中Gas-17终浓度为1~1000 nmo1/L;第2组:丙谷胺(PGL)组,培养液中PGL终浓度为0.1~10 mmol/L;第3组:17肽胃泌素+丙谷胺组(联合用药组),培养液中Gas-17终浓度为100 nmo1/L、PGL终浓度为1~10 mmol/L;以不加药培养液为对照组。采用四甲基偶氮唑盐(MTT)比色法观察各组细胞增殖活力。蛋白免疫印迹法(Western blot)测定17肽胃泌素组(培养液中Gas-17终浓度为1~100 nmo1/L),丙谷胺组(PGL终浓度为10mmol/L),联合用药组(Gas-17终浓度为100 nmo1/L、PGL终浓度为10 mmol/L)及不加药对照组中TFF1和TFF3蛋白的表达变化。结果 MTT结果显示:Gas-17在1~1000 nmo1/L时具有明显的促MKN45细胞增殖作用(P【0.05);PGL在1~10 mmol/L时有显著的抑制MKN45细胞增殖作用(P【0.05);Gas-17+PGL组中,PGL(1~10 mmol/L)能阻断并抑制Gas-17对胃癌细胞MKN45的促增殖作用(P【0.05)。Western blot结果显示:在Gas-17组中TFF1蛋白表达减弱(P【0.05),而TFF3蛋白表达增强(P【0.05);PGL组中TFF1蛋白表达增强而TFF3蛋白表达减弱;Gas-17+PGL组中,PGL能阻断Gas-17诱导的TFF1蛋白表达下调(P【0.05),阻断Gas-17诱导的TFF3蛋白表达上调(P【0.05)。结论Gas-17可诱导人胃癌细胞MKN45增殖,其受体抑制剂PGL能阻断并抑制这一作用。胃癌细胞株MKN45中有TFF1和TTF3蛋白的表达,Gas-17促进TFF1蛋白表达下调,而促进TFF3蛋白表达上调,这可能是胃泌素诱导胃癌发生发展的的机制之一。

三叶因子1表达与胃黏膜损伤及胃癌的关系

目的 测定三叶因子 1(TFF1)在正常及病理条件下胃黏膜中的表达情况 ,探讨TFF1在胃黏膜损伤修复及胃癌抑制中的作用及意义。方法 应用免疫组化方法测定正常及不同病理条件下胃黏膜中TFF1的表达情况 ,通过图像分析软件分析阳性信号平均吸光度值以了解其表达情况。结果 胃炎、胃溃疡及十二指肠球部溃疡患者TFF1表达明显高于正常胃黏膜 (0 .5 1± 0 .0 5 ,0 .5 1± 0 .0 6 ,0 .5 0± 0 .0 6比 0 .4 4± 0 .0 6 ;P值均 <0 .0 1)。胃腺癌患者癌旁组织表达 (0 .5 1± 0 .0 7)明显高于正常胃黏膜 ,而腺癌组织的表达强度则与癌组织的分化程度呈正比 ,分化程度愈低 ,表达愈弱 ,低分化腺癌无阳性表达 ,中、高分化腺癌表达 (0 .4 1± 0 .0 7)略低于正常黏膜 ,但差异无显著性 (P >0 .0 5 )。结论 TFF1表达随黏膜损伤程度的加重而表达增强 ,提示其在胃黏膜保护及促进上皮重建机制中具有一定的作用。TFF1在癌旁组织中表达增强提示其可能与肿瘤抑制及分化机制有关 ,而在癌组织中表达减弱可能与其分泌减少有关。