Your browser doesn't support javascript.
loading
Nitric oxide suppresses tumor cell migration through N-Myc downstream-regulated gene-1 (NDRG1) expression: role of chelatable iron.
Hickok, Jason R; Sahni, Sumit; Mikhed, Yuliya; Bonini, Marcelo G; Thomas, Douglas D.
Afiliación
  • Hickok JR; Departments of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois 60612.
  • Sahni S; Departments of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois 60612.
  • Mikhed Y; Departments of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois 60612.
  • Bonini MG; Departments of Medicine and Pharmacology, University of Illinois, Chicago, Illinois 60612.
  • Thomas DD; Departments of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois 60612. Electronic address: ddthomas@uic.edu.
J Biol Chem ; 286(48): 41413-41424, 2011 Dec 02.
Article en En | MEDLINE | ID: mdl-21976667
N-Myc downstream-regulated gene 1 (NDRG1) is a ubiquitous cellular protein that is up-regulated under a multitude of stress and growth-regulatory conditions. Although the exact cellular functions of this protein have not been elucidated, mutations in this gene or aberrant expression of this protein have been linked to both tumor suppressive and oncogenic phenotypes. Previous reports have demonstrated that NDRG1 is strongly up-regulated by chemical iron chelators and hypoxia, yet its regulation by the free radical nitric oxide ((•)NO) has never been demonstrated. Herein, we examine the chemical biology that confers NDRG1 responsiveness at the mRNA and protein levels to (•)NO. We demonstrate that the interaction of (•)NO with the chelatable iron pool (CIP) and the appearance of dinitrosyliron complexes (DNIC) are key determinants. Using HCC 1806 triple negative breast cancer cells, we find that NDRG1 is up-regulated by physiological (•)NO concentrations in a dose- and time-dependant manner. Tumor cell migration was suppressed by NDRG1 expression and we excluded the involvement of HIF-1α, sGC, N-Myc, and c-Myc as upstream regulatory targets of (•)NO. Augmenting the chelatable iron pool abolished (•)NO-mediated NDRG1 expression and the associated phenotypic effects. These data, in summary, reveal a link between (•)NO, chelatable iron, and regulation of NDRG1 expression and signaling in tumor cells.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Movimiento Celular / Depuradores de Radicales Libres / Proteínas de Ciclo Celular / Hierro / Óxido Nítrico / Óxidos de Nitrógeno Límite: Female / Humans Idioma: En Revista: J Biol Chem Año: 2011 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Movimiento Celular / Depuradores de Radicales Libres / Proteínas de Ciclo Celular / Hierro / Óxido Nítrico / Óxidos de Nitrógeno Límite: Female / Humans Idioma: En Revista: J Biol Chem Año: 2011 Tipo del documento: Article