Browse

Upregulation of VEGF by 15-deoxy-Δ12,14-prostaglandin J2 via heme oxygenase-1 and ERK1/2 signaling in MCF-7 cells

Cited 44 time in Web of Science Cited 47 time in Scopus
Authors
Kim, Eun-Hee; Na, Hye-Kyung; Surh, Young-Joon
Issue Date
2006-12
Citation
Annals of the New York Academy of Sciences, Vol.1090, pp.375-384
Keywords
15-deoxy-Delta(12,14)-prostaglandin J(2)heme oxygenase-1VEGFERKMCF-7 cells
Abstract
The vascular endothelial growth factor (VEGF) induces angiogenesis in ischemic or inflamed tissues during tumor growth. 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an endogenous ligand of peroxisome proliferator-activated receptor (PPAR) gamma, has been reported to upregulate VEGF synthesis through the induction of heme oxygenase (HO)-1. In this work, we found that treatment of human breast cancer (MCF-7) cells with 15d-PGJ(2) led to time-dependent increases in the expression of HO-1. The PPAR gamma antagonist GW9662 and N-acetylcysteine failed to block induction of HO-1 by 15d-PGJ2. Elevated expression or activity of HO-1 has been reported to stimulate proliferation and to accelerate angiogenesis in several tumor cells. The induction of HO-1 expression preceded the upregulation of VEGF in MCF-7 cells stimulated with 15d-PGJ2. In another experiment, 15d-PGJ2 induced phosphorylation of extracellular signal-regulated kinase (ERK1/2) in 12 h. Treatment of MCF-7 cells with U0126 or transient transfection with dominant negative ERK (DN-ERK) abrogated 15d-PGJ(2)-induced VEGF expression. To determine whether the induction of HO-1 is responsible for ERK1/2 activation, the HO-1 inhibitor, zinc protoporphyrin (ZnPP) was used. The phosphorylation of ERK1/2 by 15d-PGJ2 was abolished by ZnPP These results suggest that 15d-PGJ(2) upregulates VEGF expression via induction of HO-1 and ERK-1 and -2 phosphorylation, which may contribute to increased angiogenesis of the tumor cells.
ISSN
0077-8923
URI
https://hdl.handle.net/10371/172756
DOI
https://doi.org/10.1196/annals.1378.041
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