Alterations of the apc gene in carcinoma cell-lines and precancerous lesions of the stomach.
Alterations of the apc gene in carcinoma cell-lines and precancerous lesions of the stomach.
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癌细胞系和胃癌前病变中 apc 基因的改变。
DOI：
10.3892/ijo.7.3.587
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发表时间：
1995
影响因子：
5.2
通讯作者：
E. Tahara
中科院分区：
文献类型：
--
作者：
K. Nishimura;H. Yokozaki;K. Haruma;G. Kajiyama;E. Tahara
APC基因的体细胞突变在8个癌细胞系，12腺瘤和16肠化生的胃进行了检查。同时检测了8种肿瘤细胞系中APC mRNA和蛋白的表达。PCR-SSCP分析在25%（2/8）的癌细胞系、42%（5/12）的胃腺瘤、6%（1/16）的肠上皮化生中检测到APC基因突变。直接测序分析证实了一个癌细胞系、一个腺瘤和一个肠上皮化生粘膜中的无义突变导致产物截短，一个腺瘤中的移码突变和一个癌细胞系和三个腺瘤中的沉默突变。另外，从印戒细胞癌中建立的KATO-Ⅲ细胞系表达很低水平的APC mRNA，且不能检测到其APC蛋白。另一方面，缺失外显子7的变体APC mRNA转录物在KATO-III中的表达水平相对较高。推测APC基因的失活可能与APC mRNA转录本的变异有关。这些数据总体上提供了强有力的证据，APC基因的变化在胃癌发生的早期事件中起着重要作用，特别是在肠型胃癌中。
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.