title: 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.
authors.affiliation: Medizinische Poliklinik, Universität Würzburg, Germany. al-taie.medpoli@mail.uni-wuerzburg.de
authors.forename: Oliver Hatem
authors.initials: OH
authors.lastname: Al-Taie
authors.forename: Nurcan
authors.initials: N
authors.lastname: Uceyler
authors.forename: Ursula
authors.initials: U
authors.lastname: Eubner
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
authors.forename: Hubert
authors.initials: H
authors.lastname: Mörk
authors.forename: Michael
authors.initials: M
authors.lastname: Scheurlen
authors.forename: Regina
authors.initials: R
authors.lastname: Brigelius-Flohe
authors.forename: Katrin
authors.initials: K
authors.lastname: Schöttker
authors.forename: Josef
authors.initials: J
authors.lastname: Abel
authors.forename: Andreas
authors.initials: A
authors.lastname: Thalheimer
authors.forename: Tiemo
authors.initials: T
authors.lastname: Katzenberger
authors.forename: Bertram
authors.initials: B
authors.lastname: Illert
authors.forename: Ralf
authors.initials: R
authors.lastname: Melcher
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000008:administration & dosage; D001483:Base Sequence; D003106:Colon / Q000201:enzymology / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D012643:Selenium / Q000008:administration & dosage; D051149:Selenoprotein P; D051140:Selenoproteins; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D011506:Proteins; D012333:RNA, Messenger; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium