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结直肠癌发生过程中硒蛋白GI - GPx和SePP的表达谱分析及基因改变

Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.

作者信息

Al-Taie Oliver Hatem, Uceyler Nurcan, Eubner Ursula, Jakob Franz, Mörk Hubert, Scheurlen Michael, Brigelius-Flohe Regina, Schöttker Katrin, Abel Josef, Thalheimer Andreas, Katzenberger Tiemo, Illert Bertram, Melcher Ralf, Köhrle Josef

机构信息

Medizinische Poliklinik, Universität Würzburg, Germany.

出版信息

Nutr Cancer. 2004;48(1):6-14. doi: 10.1207/s15327914nc4801_2.

Abstract

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

摘要

微量元素硒被作为结直肠癌发生过程中的一种化学预防剂进行讨论。含硒代半胱氨酸的蛋白质,即所谓的硒蛋白,是营养性补充硒的潜在分子靶点。由于其抗氧化潜能,硒蛋白胃肠道谷胱甘肽过氧化物酶(GI-GPx)和硒蛋白P(SePP)被认为可提供针对活性氧(ROS)的保护作用,从而减少DNA损伤并预防结肠癌的发生。GI-GPx和SePP在正常结肠黏膜中大量表达。最近,我们证明在结直肠腺瘤中SePP表达降低而GI-GPx表达增加。在本研究中,我们调查了结直肠癌中SePP和GI-GPx相对于相应正常黏膜的表达情况。此外,还分析了SePP和GI-GPx基因内的基因改变情况。我们观察到结肠癌中SePP mRNA表达显著降低或缺失,而GI-GPx mRNA和蛋白质表达在不同肿瘤样本间存在差异。此外,我们在SePP和GI-GPx基因中鉴定出了新的多态性,其与蛋白质功能的相关性目前尚不清楚。我们的结果反对结直肠癌发生过程中硒蛋白表达普遍降低的观点,但提示个别硒蛋白的表达存在特定的差异调节。

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