Hamer, Isabelle; Delaive, Edouard; Dieu, Marc; Abdel-Sater, Fadi; Mercy, Ludovic; Jadot, Michel; Arnould, Thierry; Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells. ; 2009
Biology of the cell / under the auspices of the European Cell Biology Organization , Vol. 101, no. 1, p. 31-41 (2009) doi: 10.1042/BC20080043 hdl: http://hdl.handle.net/2078.2/23264

Up-regulation of cathepsin B expression and enhanced secretion in mitochondrial DNA-depleted osteosarcoma cells.

Auteur :	Hamer, Isabelle ; Delaive, Edouard ; Dieu, Marc ; Abdel-Sater, Fadi ; Mercy, Ludovic ; Jadot, Michel ; Arnould, Thierry

Résumé

BACKGROUND INFORMATION: mtDNA (mitochondrial DNA) mutations that impair oxidative phosphorylation can contribute to carcinogenesis through the increased production of reactive oxygen species and through the release of proteins involved in cell motility and invasion. On the other hand, many human cancers are associated with both the up-regulation and the increased secretion of several proteases and heparanase. In the present study, we tried to determine whether the depletion in mtDNA could modulate the expression and/or the secretion of some lysosomal hydrolases in the 143B osteosarcoma cells, as these mtDNA-depleted cells are characterized by a higher degree of invasiveness than the parental cells. RESULTS: In comparison with the parental cells, we measured a higher amount of procathepsin B in the conditioned culture medium of the 143B cells lacking mtDNA (rho(0) 143B cells), as well as a rise in the specific activity of intracellular cathepsin B. In addition, we observed an activation of the transcription factor NF-kappaB (nuclear factor kappaB) in the cells devoid of functional mitochondria. Finally, we demonstrated that the down-regulation of the NF-kappaB p65 subunit by RNA interference led to a reduction in cathepsin B expression in rho(0) 143B cells. CONCLUSIONS: The up-regulation of cathepsin B by NF-kappaB, followed by its secretion into the extracellular environment, might be partly responsible for the previously reported invasiveness of the mtDNA-depleted 143B osteosarcoma cells.

Informations complémentaires

Departement :	FUNDP
Type :	Article de périodique (Journal article)
MESH :	Cathepsin B - genetics - secretion ; Cell Line, Tumor ; DNA, Mitochondrial ; Humans ; NF-kappa B - metabolism ; Neoplasm Invasiveness - pathology ; Osteosarcoma - pathology ; RNA, Small Interfering - pharmacology ; Transcription Factor RelA - deficiency - drug effects ; Up-Regulation - genetics ;
Source :	"Biology of the cell / under the auspices of the European Cell Biology Organization" - Vol. 101, no. 1, p. 31-41 (2009)
issn :	0248-4900
e-issn :	1768-322X
Texte intégral :	10.1042/BC20080043
Lien(s) :	http://www.ncbi.nlm.nih.gov/pubmed/18598236
Date de publication :	2009

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