Sawaya Manabu, Yoshimura Tetsuro, Shimoyama Tadashi, Munakata Akihiro, Fukuda Shinsaku
First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Japan.
J Clin Gastroenterol. 2008 Apr;42(4):351-5. doi: 10.1097/MCG.0b013e318054493e.
To examine the significance of alteration of p53-regulated apoptosis-induced protein 1 (p53AIP1) expression in gastric carcinogenesis in patients with Helicobacter pylori infection.
H. pylori infection induces gastric mucosal inflammation and DNA damage of epithelial cells, which associate with gastric carcinogenesis. p53AIP1 is expressed after DNA damage and induces apoptosis in human cell lines.
Endoscopic antral and corpus biopsies were obtained from 13 patients with chronic gastritis and 17 with gastric cancer. Expression of p53AIP1 and p53DINP1 mRNA was examined by semiquantitative reverse transcription polymerase chain reaction and mutation of p53 codon-46 was studied by direct sequence analysis. The grade of gastritis was assessed according to the updated Sydney System. Results were compared between patients with gastric cancer and chronic gastritis.
In the antrum, p53AIP1 mRNA expression was significantly lower in patients with gastric cancer than in those with chronic gastritis (P<0.05). In patients with chronic gastritis, expression of p53AIP1 mRNA was significantly higher in the antrum than in the corpus (P<0.05). In patients with chronic gastritis, antral mucosa with high p53AIP1 expression tended to have severe intestinal metaplasia. No mutation was found at p53 codon-46.
In H. pylori-infected gastric mucosa expression of p53AIP1 would be higher when the inflammation is severe or intestinal metaplasia is present. Insufficient expression of p53AIP1 may play a role in gastric carcinogenesis in patients infected with H. pylori infection.
研究幽门螺杆菌感染患者中p53调控的凋亡诱导蛋白1(p53AIP1)表达改变在胃癌发生中的意义。
幽门螺杆菌感染可诱导胃黏膜炎症和上皮细胞DNA损伤,这与胃癌发生相关。p53AIP1在DNA损伤后表达,并在人细胞系中诱导凋亡。
对13例慢性胃炎患者和17例胃癌患者进行内镜下胃窦和胃体活检。采用半定量逆转录聚合酶链反应检测p53AIP1和p53DINP1 mRNA的表达,并通过直接序列分析研究p53密码子46的突变情况。根据更新后的悉尼系统评估胃炎分级。比较胃癌患者和慢性胃炎患者的结果。
在胃窦部,胃癌患者的p53AIP1 mRNA表达明显低于慢性胃炎患者(P<0.05)。在慢性胃炎患者中,胃窦部的p53AIP1 mRNA表达明显高于胃体部(P<0.05)。在慢性胃炎患者中,p53AIP1表达高的胃窦黏膜往往有严重的肠化生。未发现p53密码子46处的突变。
在幽门螺杆菌感染的胃黏膜中,当炎症严重或存在肠化生时,p53AIP1的表达会更高。p53AIP1表达不足可能在幽门螺杆菌感染患者的胃癌发生中起作用。