Reduced expression of p33ING1 and the relationship with p53 expression in human gastric cancer
Reduced expression of p33ING1 and the relationship with p53 expression in human gastric cancer
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DOI：
10.1016/s0304-3835(99)00288-8
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发表时间：
1999-12-01
期刊：
影响因子：
9.7
通讯作者：
Sugimachi, K
中科院分区：
文献类型：
--
作者：
Oki, E;Maehara, Y;Sugimachi, K
p33（ING 1）是一种新的肿瘤抑制基因的候选生长抑制因子。p33（ING 1）与p53合作，通过激活p21/WAF 1启动子的转录来负调节细胞生长，即使它与p53没有显著的序列相似性。我们首先采用定量RT-PCR和实时TaqmanTM技术比较了p33（ING 1）在人胃癌和配对正常组织中的表达。20例胃癌中有15例p33（ING 1）表达明显降低。在免疫组化分析中，20例肿瘤中有4例（20%）检测到p53蛋白表达，15例（80%）在RT-PCR中p33（ING 1）表达降低的肿瘤中有12例（80%）具有野生型p53。我们检测了12个胃肠道癌细胞系中p33（ING 1）基因的序列，仅在一个细胞系HCT 116中发现了突变。我们的研究结果被解释为意味着p33（ING 1）可能作为一个肿瘤抑制在胃癌发生，即使该基因是保存在大多数胃肠道癌。值得注意的是，p33的表达在许多癌症患者中降低，p33（ING 1）和p53的生物学效应是相互关联的，需要两种基因的活性。(C)1999爱思唯尔科学爱尔兰有限公司版权所有。
p33(ING1) is a novel growth inhibitor candidate for a tumor suppressor gene. p33(ING1) cooperates with p53 and negatively regulates cell growth by activating transcription from the p21/WAF1 promoter even though it has no significant sequence similarity to p53. We first compared p33(ING1) expression in human gastric cancers and matched normal tissues using quantitative RT-PCR and realtime 'Taqman TM' technology. A significant decrease in p33(ING1) expression was evident in 15 of 20 gastric cancers. In immunohistochemical analysis, p53 protein expression was detected in 4 of 20 (20%) tumors, and 12 of 15 (80%) tumors with decreasing p33(ING1) expression in RT-PCR had the wild type p53. When we examined the sequence of p33(ING1) in 12 gastrointestinal carcinoma cell lines, we found mutation in only one cell line, HCT116. Our findings are interpreted to mean that p33(ING1) may function as a tumor suppressor in gastric carcinogenesis, even though the gene is preserved in the majority of gastrointestinal carcinomas. It should be noted that expression of p33 decreased in many cancer patients, and the biological effects of p33(ING1) and p53 are interrelated and require the activity of both genes. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.