Nishimura K, Yokozaki H, Haruma K, Kajiyama G, Tahara E
HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,MINAMI KU,HIROSHIMA 734,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED 1,MINAMI KU,HIROSHIMA 734,JAPAN.
Int J Oncol. 1995 Sep;7(3):587-92. doi: 10.3892/ijo.7.3.587.
Somatic mutations of the APC gene in eight cancer cell lines, twelve adenomas and sixteen intestinal metaplasias of the stomach were examined. The expression of the APC mRNA and protein in eight cancer cell lines was also investigated. PCR-SSCP analysis detected mutations of the APC gene in 25% (2 out of 8) of cancer cell lines, 42% (5 out of 12) of gastric adenomas, 6% (1 out of 16) of intestinal metaplasia mucosae. Direct sequencing analysis confirmed nonsense mutations in one cancer cell line, one adenoma and one intestinal metaplasia mucosa resulted in truncation of the product, frameshift mutations in one adenoma and silent mutations in one cancer cell line and three adenomas. In addition, the KATO-III cell line, which was established from signet ring cell carcinoma, expressed very low level of APC mRNA and its APC protein could not be detected. On the other hand, the expression level of variant APC mRNA transcript which lacks exon 7 was relatively high in KATO-III. It is supposed that the variant APC mRNA transcript might contribute to the inactivation of the APC gene. These data overall provide strong evidence that changes in the APC gene play an important role in the early event of stomach carcinogenesis, especially in intestinal type gastric cancer.
检测了8种癌细胞系、12个腺瘤以及16个胃黏膜肠化生组织中APC基因的体细胞突变情况。同时也研究了8种癌细胞系中APC mRNA和蛋白的表达情况。PCR-SSCP分析检测到，在25%（8个中的2个）的癌细胞系、42%（12个中的5个）的胃腺瘤以及6%（16个中的1个）的肠化生黏膜中存在APC基因的突变。直接测序分析证实，在一个癌细胞系、一个腺瘤和一个肠化生黏膜中存在无义突变，导致产物截短；在一个腺瘤中存在移码突变；在一个癌细胞系和三个腺瘤中存在沉默突变。此外，从印戒细胞癌建立的KATO-III细胞系中，APC mRNA表达水平极低，且未检测到其APC蛋白。另一方面，在KATO-III中，缺失外显子7的变异APC mRNA转录本的表达水平相对较高。推测该变异APC mRNA转录本可能导致了APC基因的失活。总体而言，这些数据有力地证明了APC基因的改变在胃癌发生的早期事件中，尤其是在肠型胃癌中发挥着重要作用。
