Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival
Thioredoxin, a putative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival
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DOI：
10.1053/hp.2000.6546
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发表时间：
2000-04-01
期刊：
影响因子：
3.3
通讯作者：
Powis, G
中科院分区：
文献类型：
--
作者：
Grogan, TM;Fenoglio-Prieser, C;Powis, G
人硫氧还蛋白是一种假定的癌基因，可赋予肿瘤细胞生长和存活优势。在原发性人肺癌和结直肠癌中均发现过表达的硫氧还蛋白mRNA。为了确定硫氧还蛋白蛋白在人原发性癌中的分布和量，我们开发了一种石蜡包埋组织中硫氧还蛋白的免疫组织化学测定法。然后，我们研究了10例原发性高危胃癌患者。为了进一步将硫氧还蛋白过度表达与细胞死亡和存活联系起来，我们使用了基于石蜡的原位末端标记（ISEL）分析。为了描述增殖，我们使用Ki-67检测的核增殖抗原。在这项调查中，我们发现，硫氧还蛋白定位于肿瘤细胞和过表达相比，正常胃粘膜在8 10胃癌。硫氧还蛋白在8例高表达癌中有5例高表达。硫氧还蛋白的过度表达通常在肿瘤细胞的细胞核和细胞质中发现。有一个显着的正相关性（P = 0.0061）与癌细胞增殖Ki-67测量。有一个显着的负相关性（P = 0.0001）与DNA损伤的ISEL测定，表明减少细胞凋亡和增加癌细胞存活。因此，与不表达硫氧还蛋白的肿瘤相比，高度表达硫氧还蛋白的人原发性胃肿瘤具有更高的增殖率和更高的存活率。有了这些新开发的检测方法，现在可以质疑硫氧还蛋白相关的生长和存活优势是否会转化为不良的临床结果。《人文哲学》31：475 - 481，2000年。Copyright（C）2000 by W.B.桑德斯公司
Human thioredoxin is a putative oncogene that may confer both a growth and survival advantage to tumor cells. Overexpressed thioredoxin mRNA has been found in both primary human lung and colorectal cancers. To determine the intratumor distribution and amount of thioredoxin protein in human primary carcinomas, we developed an immunohistochemical assay for thioredoxin in paraffin-embedded tissue. We then studied 10 patients with primary high-risk gastric carcinoma. To further relate thioredoxin protein overexpression to cell death and survival, we used a paraffin-based in situ end-labeling (ISEL) assay. To delineate proliferation, we used the nuclear proliferation antigen detected by Ki-67. In this survey, we found that thioredoxin was localized to tumor cells and overexpressed compared with normal gastric mucosa in 8 of 10 gastric carcinomas. The thioredoxin was found at high levels in 5 of the 8 overexpressing carcinomas. The overexpression of thioredoxin was typically found in both a nuclear and cytoplasmic location in the neoplastic cells. There was a significant positive correlation (P = .0061) with cancer cell proliferation measured by Ki-67. There was a significant negative correlation (P = .0001) with DNA damage measured by the ISEL assay, suggesting decreased apoptosis and increased carcinoma cell survival. Thus, human primary gastric tumors that are highly expressive of thioredoxin have both a higher proliferative rate and a higher survival rate than tumors that do not express thioredoxin. With these newly developed assays in hand, it is now feasible to question whether this: thioredoxin-related combined growth and survival advantage translates into poor clinical outcome. HUM PATHOL 31:475-481, 2000. Copyright (C) 2000 by W.B. Saunders Company.