Lincoln David T, Ali Emadi Eman M, Tonissen Kathryn F, Clarke Frank M
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, P.O. BOX 31470, 90805 Sulaibikhat, Kuwait.
Anticancer Res. 2003 May-Jun;23(3B):2425-33.
Redox control has emerged as a fundamental biological control mechanism. One of the major redox control systems is the thioredoxin system comprised of thioredoxin (TRX) and thioredoxin reductase (TR). Together they form a powerful system involved in many central intracellular and extracellular processes including cell proliferation, the redox regulation of gene expression and signal transduction, protection against oxidative stress, anti-apoptotic functions, growth factor and co-cytokine effects, and regulation of the redox state of the extracellular environment. Over recent years this system has increasingly been linked to the development and expression of cancer phenotypes. In this report immunocytochemical approaches have been used to simultaneously determine the expression and localisation of both TRX and TR in primary human cancers, including breast cancer, thyroid, prostate and colorectal carcinoma, and malignant melanoma. In aggressive invasive mammary carcinomas and advanced malignant melanomas, thioredoxin was highly over-expressed compared to tumours of lesser aggressive nature. TRX expression was found in both nuclear and cytoplasmic location in the neoplastic cells. Furthermore, increased levels of TRX positively correlate with thioredoxin reductase (TR) expression and localisation. These results, which are the first immunocytochemical studies on the in vivo expression and localisation of TRX and TR in melanomas, thyroid, prostate and colorectal carcinomas and the first reports of TR expression in breast carcinomas, significantly extend the range of human cancers for which such data is available. Overall the results support the conclusion that aggressive tumours greatly over-express both TRX and TR. Such tumours have a high proliferation capacity, a low apoptosis rate and an elevated metastatic potential strongly implicating the involvement of the TRX system in the processes of oncogenesis and tumourogenesis and confirming its potential as a target for anticancer therapy for a wide range of human tumours.
氧化还原调控已成为一种基本的生物调控机制。主要的氧化还原调控系统之一是由硫氧还蛋白（TRX）和硫氧还蛋白还原酶（TR）组成的硫氧还蛋白系统。它们共同构成了一个强大的系统，参与许多重要的细胞内和细胞外过程，包括细胞增殖、基因表达的氧化还原调节和信号转导、抗氧化应激保护、抗凋亡功能、生长因子和辅助细胞因子作用以及细胞外环境氧化还原状态的调节。近年来，该系统越来越多地与癌症表型的发展和表达相关联。在本报告中，免疫细胞化学方法被用于同时测定TRX和TR在原发性人类癌症中的表达和定位，这些癌症包括乳腺癌、甲状腺癌、前列腺癌、结直肠癌和恶性黑色素瘤。在侵袭性强的浸润性乳腺癌和晚期恶性黑色素瘤中，与侵袭性较弱的肿瘤相比，硫氧还蛋白高度过表达。在肿瘤细胞中发现TRX表达于细胞核和细胞质中。此外，TRX水平的升高与硫氧还蛋白还原酶（TR）的表达和定位呈正相关。这些结果是关于TRX和TR在黑色素瘤、甲状腺癌、前列腺癌和结直肠癌中体内表达和定位的首次免疫细胞化学研究，也是乳腺癌中TR表达的首次报道显著扩展了有此类数据的人类癌症范围。总体而言，这些结果支持以下结论：侵袭性肿瘤大量过表达TRX和TR。此类肿瘤具有高增殖能力、低凋亡率和高转移潜能，强烈提示硫氧还蛋白系统参与肿瘤发生和发展过程，并证实其作为多种人类肿瘤抗癌治疗靶点的潜力。
