title: The 15kDa selenoprotein and thioredoxin reductase 1 promote colon cancer by different pathways.
abstract: Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.
authors.affiliation: Department of Biological Sciences, Towson University, Towson, Maryland, United States of America.
authors.forename: Petra A
authors.initials: PA
authors.lastname: Tsuji
authors.affiliation: Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.affiliation: Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Min-Hyuk
authors.initials: MH
authors.lastname: Yoo
authors.affiliation: Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Salvador
authors.initials: S
authors.lastname: Naranjo-Suarez
authors.affiliation: Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Xu
authors.affiliation: Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: He
authors.affiliation: Center for Information Technology, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Esther
authors.initials: E
authors.lastname: Asaki
authors.affiliation: Nutritional Science Research Group, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Seifried
authors.affiliation: Genomics & Informatics Group, Laboratory of Molecular Pharmacology, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Reinhold
authors.affiliation: Office of Dietary Supplements, National Institutes of Health, Rockville, Maryland, United States of America.
authors.forename: Cindy D
authors.initials: CD
authors.lastname: Davis
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.affiliation: Molecular Biology of Selenium Section, Mouse Cancer Genetics Program, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D020869:Gene Expression Profiling; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C495239:Selenof protein, mouse; D051140:Selenoproteins; D054481:Thioredoxin Reductase 1