Browse

TNF-α induces expression of urokinase-type plasminogen activator and β-catenin activation through generation of ROS in human breast epithelial cells

Cited 26 time in Web of Science Cited 27 time in Scopus
Authors
Kim, Min-Jung; Kim, Do-Hee; Na, Hye-Kyung; Surh, Young-Joon
Issue Date
2010-12
Citation
Biochemical Pharmacology, Vol.80 No.12, pp.2092-2100
Keywords
MetastasisTNF-alphaROSMCF-10A cellsuPAbeta-CateninEupatilin
Abstract
Malignant tumors have a capability to degrade the extracellular matrix (ECM) by controlled proteolysis. One of the important components of the proteolysis system involved in such process is urokinase-type plasminogen activator (uPA). Tumor necrosis factor (TNF)-alpha was found to stimulate uPA. TNF-alpha impaired the ability of cells to aggregate and to attain compaction. Dyscohesion (cell-cell dissociation) induced by TNF-alpha was associated with the disordered expression of cadherin/beta-catenin at the sites of cell-cell contact. We observed that human breast epithelial (MCF-10A) cells treated with TNF-alpha transiently up-regulated expression of uPA and its mRNA transcript. In addition, TNF-alpha induced activation of beta-catenin in MCF-10A cells. Based on these findings, we attempted to examine the role of beta-catenin and its partner, Tcf-4 in upregulation of uPA. siRNA knock down of beta-catenin abrogated TNF-alpha-induced uPA expression as well as Tcf-4/beta-catenin DNA binding. TNF-alpha-stimulated MCF-10A cells exhibited increased intracellular accumulation of reactive oxygen species (ROS). TNF-alpha-induced expression of uPA and activation of beta-catenin signaling appear to be mediated by ROS in MCF-10A cells, as both events were blocked by the antioxidant N-acetylcysteine. Eupatilin (5,7-dihydroxy-3',4',6-tri-methoxy-flavone), a pharmacologically active flavone derived from Artemisia asiatica, has been shown to possess strong antioxidative activity. Eupatilin inhibited TNF-alpha-induced intracellular ROS accumulation, expression of uPA and beta-catenin activation. Moreover, eupatilin inhibited the TNF-alpha-induced invasion of MCF-10A cells. Taken together, the above results suggest that eupatilin has chemopreventive effects on mammary tumorigenesis by targeting the beta-catenin-uPA axis stimulated by TNF-alpha. (C) 2010 Published by Elsevier Inc.
ISSN
0006-2952
URI
https://hdl.handle.net/10371/172594
DOI
https://doi.org/10.1016/j.bcp.2010.08.014
Files in This Item:
There are no files associated with this item.
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse