同源结构域蛋白CDX2在胆囊癌中的表达。
Expression of homeodomain protein CDX2 in gallbladder carcinomas.
作者信息
Wu Xiang-Song, Akiyama Yoshimitsu, Igari Toru, Kawamura Tohru, Hiranuma Susumu, Shibata Toshikatsu, Tsuruta Kouji, Koike Morio, Arii Shigeki, Yuasa Yasuhito
机构信息
Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
出版信息
J Cancer Res Clin Oncol. 2005 May;131(5):271-8. doi: 10.1007/s00432-004-0658-4. Epub 2005 Jan 11.
PURPOSE
Caudal-related homeobox protein CDX2 plays an important role in the regulation of cell proliferation and differentiation of the intestinal epithelium. CDX2 is associated with intestinal metaplasia and carcinomas of the stomach, but the role of CDX2 in gallbladder carcinogenesis remains unknown.
METHODS
We analyzed the expression of CDX2 and intestinal apomucin MUC2 in gallbladder cancer cell lines at the mRNA level by the RT-PCR method. We also investigated the expression of CDX2 and MUC2 in 68 primary gallbladder carcinomas by the immunohistochemical staining method and compared the expression of CDX2 with the clinicopathological factors in the gallbladder carcinoma cases.
RESULTS
Expression of CDX2 and MUC2 was found in three of four gallbladder cancer cell lines at the mRNA level. In addition, we found that CDX2 was absent in the normal gallbladder epithelium, but the CDX2 protein was expressed in 25 of the 68 (36.8%) gallbladder carcinomas. Interestingly, in the tubular type gallbladder carcinomas, the frequency of CDX2 expression was much higher in the well-differentiated type than the moderately and poorly differentiated types, the difference being statistically significant (P<0.01). CDX2 expression showed a relationship with expression of MUC2 (P<0.04) in the gallbladder carcinomas. CDX2 was expressed in intestinal metaplasia and dysplasia, which are hypothesized to be premalignant conditions.
CONCLUSION
These results imply that CDX2 plays an important role in gallbladder carcinogenesis with intestinal differentiation.
目的
尾型相关同源框蛋白CDX2在肠道上皮细胞增殖和分化的调控中起重要作用。CDX2与肠化生及胃癌相关，但CDX2在胆囊癌发生中的作用尚不清楚。
方法
我们采用RT-PCR方法在mRNA水平分析了CDX2和肠型黏蛋白MUC2在胆囊癌细胞系中的表达。我们还通过免疫组织化学染色方法研究了68例原发性胆囊癌中CDX2和MUC2的表达情况，并将胆囊癌病例中CDX2的表达与临床病理因素进行了比较。
结果
在4个胆囊癌细胞系中的3个中检测到了CDX2和MUC2在mRNA水平的表达。此外，我们发现正常胆囊上皮中不存在CDX2，但在68例（36.8%）胆囊癌中有25例表达CDX2蛋白。有趣的是，在管状型胆囊癌中，高分化型CDX2表达频率明显高于中分化型和低分化型，差异有统计学意义（P<0.01）。胆囊癌中CDX2表达与MUC2表达有关（P<0.04）。CDX2在肠化生和发育异常中表达，而肠化生和发育异常被认为是癌前病变。
结论
这些结果表明CDX2在胆囊癌伴肠化生的发生中起重要作用。
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