Expression Profiling and Genetic Alterations of the Selenoproteins GI-GPx and SePP in Colorectal Carcinogenesis

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.

Variation in the Selenoenzyme Genes and Risk of Advanced Distal Colorectal Adenoma

“…SEPP1 contains 10 selenocysteines and is the only selenoprotein with more than one selenocysteine. SEPP1 binds f40% to 60% of the selenium in plasma and is found in several tissues, including the colon, where it becomes down-regulated during tumor development (26,(47)(48)(49). SEPP1 has three important functions: transport of selenium to target tissues, intracellular selenium binding and supply, and protection against oxidative stress (47,(50)(51)(52)(53)(54).…”

Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage

“…Selenium has been identifact that, even under conditions of severe selenium deficiency, its production perseveres (19). Previous studies have shown that SEPP1 is downregulated in colorectal cancers (CRCs) (21) and SNPs within the gene are associated with advanced adenoma risk (22). Because SEPP1 serves as the major selenium transport protein, the known effects of selenium on WNT and NRF2 signaling in target tissues may partially depend on SEPP1.…”

Tissue Microarray Assessment of Selenoprotein P Expression in Gastric Adenocarcinoma

“…4 Supplementation with Se has also been shown to resist and reduce the carcinogenic effects of mutagens and carcinogens. 7 It can also block pre-cancerous lesions, 8 and Se supplementation has been reported to increase natural killer cell counts before surgical operation. 9 The level of SelP expression in gastric mucosa infected by Helicobacter pylori correlated negatively with expression of proliferating cell nuclear antigen, but correlated positively with expression of P16.…”