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Nutr Cancer. 2004;48(1):6-14.

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

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1
Medizinische Poliklinik, Universität Würzburg, Germany. al-taie.medpoli@mail.uni-wuerzburg.de

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.

PMID:
15203372
DOI:
10.1207/s15327914nc4801_2
[Indexed for MEDLINE]
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