Xiang Y Y, Wang D Y, Tanaka M, Suzuki M, Kiyokawa E, Igarashi H, Naito Y, Shen Q, Sugimura H
First Department of Pathology, Hamamatsu University School of Medicine, Japan.
Int J Cancer. 1997 Feb 20;74(1):1-6. doi: 10.1002/(sici)1097-0215(19970220)74:1<1::aid-ijc1>3.0.co;2-6.
An 1194-nucleotide complementary DNA clone, FM1, encoding a human high-mobility group-1 protein (HMG-1) was isolated from a well-differentiated human gastric-carcinoma cell line complementary DNA library by a differential screening method. FM1 is similar to the published human HMG-1 in mature protein, with only 3 different codons at positions 11, 149, and 190. We analyzed 33 gastric and colorectal adenocarcinomas for expression of the FM1 gene. Northern-blot analysis revealed that all of the cancers expressed FM1 at a higher level than in corresponding non-cancerous mucosa, with 2 transcripts of approximately 1.4 and 2.4 kilobases. The FM1 expression level in the non-cancerous tissues increased with the depth of accompanying cancer invasion. Only 18.2% of well-differentiated cancers showed a higher expression level in corresponding non-cancerous tissues, whereas the expression in corresponding non-cancerous tissues was significantly higher in moderately (60%) and poorly differentiated (83.3%) cancers. In situ hybridization demonstrated the location of FM1 mRNA in well- and poorly differentiated gastric-cancer cells as well as in non-cancerous tissue adjacent to poorly differentiated gastric cancer, but no hybridization was detected in normal epithelial cells adjacent to well-differentiated gastric cancer. These findings may provide new information on HMG-1 mRNA expression in human gastrointestinal cancer and suggest a correlation between FM1 mRNA expression to the differentiation and the stage of human gastrointestinal adenocarcinomas.
通过差异筛选法,从一个高分化人胃癌细胞系互补DNA文库中分离出一个1194个核苷酸的互补DNA克隆FM1,其编码人高迁移率族蛋白1(HMG-1)。FM1在成熟蛋白方面与已发表的人HMG-1相似,仅在第11、149和190位有3个不同的密码子。我们分析了33例胃和结肠腺癌中FM1基因的表达情况。Northern杂交分析显示,所有癌症中FM1的表达水平均高于相应的非癌黏膜,有两条约1.4和2.4千碱基的转录本。非癌组织中FM1的表达水平随伴随癌症浸润深度的增加而升高。仅18.2%的高分化癌症在相应的非癌组织中显示出较高的表达水平,而在中分化(60%)和低分化(83.3%)癌症中,相应非癌组织中的表达明显更高。原位杂交显示FM1 mRNA在高分化和低分化胃癌细胞以及低分化胃癌旁的非癌组织中定位,但在高分化胃癌旁的正常上皮细胞中未检测到杂交信号。这些发现可能为人类胃肠道癌中HMG-1 mRNA的表达提供新信息,并提示FM1 mRNA表达与人类胃肠道腺癌的分化和分期之间存在相关性。