title: Selenium-binding protein 1: its physiological function, dependence on aryl hydrocarbon receptors, and role in wasting syndrome by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
abstract: BACKGROUND
  Selenium-binding protein 1 (Selenbp1) is suggested to play a role in tumor suppression, and may be involved in the toxicity produced by dioxin, an activator of aryl hydrocarbon receptors (AhR). However, the mechanism or likelihood is largely unknown because of the limited information available about the physiological role of Selenbp1.
  
  
  METHODS
  To address this issue, we generated Selenbp1-null [Selenbp1 (-/-)] mice, and examined the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in this mouse model.
  
  
  RESULTS
  Selenbp1 (-/-) mice exhibited only a few differences from wild-type mice in their apparent phenotypes. However, a DNA microarray experiment showed that many genes including Notch1 and Cdk1, which are known to be enhanced in ovarian carcinoma, are also increased in the ovaries of Selenbp1 (-/-) mice. Based on the different responses to TCDD between C57BL/6J and DBA/2J strains of mice, the expression of Selenbp1 is suggested to be under the control of AhR. However, wasting syndrome by TCDD occurred equally in Selenbp1 (-/-) and (+/+) mice.
  
  
  CONCLUSIONS
  The above pieces of evidence suggest that 1) Selenbp1 suppresses the expression of tumor-promoting genes although a reduction in Selenbp1 alone is not very serious as far as the animals are concerned; and 2) Selenbp1 induction by TCDD is neither a pre-requisite for toxicity nor a protective response for combating TCDD toxicity.
  
  
  CONCLUSIONS
  Selenbp1 (-/-) mice exhibit little difference in their apparent phenotype and responsiveness to dioxin compared with the wild-type. This may be due to the compensation of Selenbp1 function by a closely-related protein, Selenbp2.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Tsujimoto
authors.forename: Takumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takeda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.forename: Yuko
authors.initials: Y
authors.lastname: Onomura
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Tsukimori
authors.forename: Shinji
authors.initials: S
authors.lastname: Takechi
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.forename: Satoshi O
authors.initials: SO
authors.lastname: Suzuki
authors.forename: Midori
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masaru
authors.initials: M
authors.lastname: Himeno
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010051:Ovarian Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects / Q000494:pharmacology; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D051137:Selenium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013723:Teratogens / Q000494:pharmacology*; D019282:Wasting Syndrome / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism*
chemical_list: C497762:Notch1 protein, mouse; D000072317:Polychlorinated Dibenzodioxins; D051881:Receptor, Notch1; D018336:Receptors, Aryl Hydrocarbon; C495176:Selenbp1 protein, mouse; D051137:Selenium-Binding Proteins; D013723:Teratogens; D016203:CDC2 Protein Kinase