Molecular Analysis for the involvment of Helicobacter Pylori in carcinogenis of oral cancer

考虑到幽门螺杆菌感染与口腔癌之间的可能联系，我们首次克隆了幽门螺杆菌膜蛋白1基因(Hp-MP1)。由于Hp-MP1可诱导炎性细胞因子的释放，而肿瘤坏死因子-α既是Hp的启动子又是肿瘤的促进剂，因此我们研究了Hp-MP1在Hp致癌中的可能作用。将Hp-MP1、Urease B基因或载体分别导入BALB/3T3细胞(对照组)和v-Ha-ras基因转染组(BALB/3T3细胞)。所有BHAS/MPL克隆均强表达肿瘤坏死因子-α基因，并在100%裸鼠体内成瘤。两个BHAS/URE克隆具有较弱的致瘤性，其他BHAS和BALB克隆均未显示出致瘤性。结果表明，Hp-MP1与病毒RAS蛋白协同具有较强的致癌活性，而与尿素酶B的活性较弱。我们发现50%的口腔扁平苔藓患者感染幽门螺杆菌。因此，我们对根除幽门螺杆菌的疗效进行了分析。5例幽门螺杆菌感染的口腔扁平苔藓患者接受根除治疗。3例在3个月内有效，2例6个月后出现疼痛。仅1例有效12个月。5例中2例无效。因此，幽门螺杆菌感染与口腔扁平苔藓之间存在一定的相关性。

Considering a suspected link between Helicobacter pylori infection and human oral cancer, we had cloned a new H.pylori gene for membrane protein 1 (HP-MP1) at first. Because HP-MP1 induces release of inflammatory cytokines and tumor necrosis factor-alpha acts as both initiator and tumor promoter, we studied the possible involvment of HP-MP1 in carcinogenesis of H.pylori. Two cell lines, BALB/3T3 cells as control and v-Ha-ras-transfected BALB/3T3 cells as putative initiated cells, were each transfected with HP-MP1, urease B genes, or vector alone. All of the Bhas/mpl clones showed strong expression of tumor necrosis factor-alpha gene and produced tumors in 100 % of nude mice. Two Bhas/ure clones showed weak tumorigenicity ; the other Bhas and BALB clones showed none. Results indicate strong carcinogenic activity of HP-MP1 in cooperation with viral Ras protein and weak activity of urease B.Secondly, we often see the changes Oral lichen planus(OLP) for cancer. We found that 50 % of OLP patients infected with H.pylori. So, we analyzed the effect the eradication therapy for H.pylori. 5 OLP patients who had H.pylori infection treated with the eradication therapy. 3 of 5 patients were effective for 3 months, but 2 of 3 patients complaned pain 6 months later. Only one patient was effective for 12months. 2 of 5 patients were not effective at all. Thus, it is considerd that there is ho relationship between H.pylori infection and OLP.