Kitamura S, Kondo S, Shinomura Y, Isozaki K, Kanayama S, Higashimoto Y, Minami T, Kiyohara T, Yasunaga Y, Ishikawa H, Ohtani T, Ishiguro S, Matsuzawa Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan.
Inflamm Res. 2000 Jul;49(7):320-4. doi: 10.1007/PL00000212.
This study was designed to determine if the hepatocyte growth factor (HGF)-Met system is involved in the repair process of inflamed mucosa of ulcerative colitis (UC) and in the development of UC-associated colorectal cancer.
HGF and c-met gene expressions were quantified in colonic mucosal specimens from healthy control subjects, patients with UC and patients with UC-associated colorectal cancer, using the competitive reverse transcription-polymerase chain reaction. Expression of HGF protein was determined by immunoblot analysis. Expression of c-Met protein was analyzed immunohistochemically.
HGF and c-met gene expressions were increased in inflamed mucosa of UC, compared with control subjects. Gene expression of HGF was also increased in the surrounding inflamed mucosa of UC-associated cancers. In cases in which the HGF gene expression was increased, an apparent increase in protein levels of HGF in inflamed mucosa of UC were observed by immunoblot analysis. The c-met gene was overexpressed in UC-associated cancers and a high level of immunoreactivity of the c-Met protein was immunohistochemically detected within the cancer cells.
We showed that HGF and c-met expression is increased in the inflamed mucosa of UC and that c-met is overexpressed in UC-associated colorectal cancers. These observations suggest HGF-Met system is involved in the repair process of the inflamed mucosa of UC and provide further support for the view that the inappropriate expressions of both HGF and c-met genes predispose to the development of colorectal cancer in patients with UC.
本研究旨在确定肝细胞生长因子（HGF）-Met系统是否参与溃疡性结肠炎（UC）炎症黏膜的修复过程以及UC相关结直肠癌的发生发展。
采用竞争性逆转录-聚合酶链反应，对健康对照者、UC患者以及UC相关结直肠癌患者的结肠黏膜标本中的HGF和c-met基因表达进行定量分析。通过免疫印迹分析确定HGF蛋白的表达，采用免疫组织化学方法分析c-Met蛋白的表达。
与对照者相比，UC炎症黏膜中的HGF和c-met基因表达增加。在UC相关癌周围的炎症黏膜中，HGF基因表达也增加。在HGF基因表达增加的病例中，通过免疫印迹分析观察到UC炎症黏膜中HGF蛋白水平明显升高。c-met基因在UC相关癌中过表达，免疫组织化学检测到癌细胞内c-Met蛋白具有高水平的免疫反应性。
我们发现UC炎症黏膜中HGF和c-met表达增加，且c-met在UC相关结直肠癌中过表达。这些观察结果表明HGF-Met系统参与UC炎症黏膜的修复过程，并进一步支持了HGF和c-met基因的不适当表达易导致UC患者发生结直肠癌这一观点。
