Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis.
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.
Al-Taie
Oliver Hatem
OH
Medizinische Poliklinik, Universität Würzburg, Germany. al-taie.medpoli@mail.uni-wuerzburg.de
Uceyler
Nurcan
N
Eubner
Ursula
U
Jakob
Franz
F
Mörk
Hubert
H
Scheurlen
Michael
M
Brigelius-Flohe
Regina
R
Schöttker
Katrin
K
Abel
Josef
J
Thalheimer
Andreas
A
Katzenberger
Tiemo
T
Illert
Bertram
B
Melcher
Ralf
R
Köhrle
Josef
J
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
D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D011506:Proteins; D012333:RNA, Messenger; D051149:Selenoprotein P; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium