Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 36
15-Deoxy-&12,14-prostaglandin J2-mediated upregulation of heme oxygenase-1 and
vascular endothelial growth factor in human breast cancer cells : a potential role of Nrf2
Eun-Hee Kim, Hye-Kyung Na and Young-Joon Surh
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention,
College of Pharmacy, Seoul National University, Seoul 151-742, South Korea
Elevated expression or activity of heme oxygenase-1 (HO-1), a ubiquitous stress-responsive
enzyme, has been reported to stimulate proliferation and to accelerate angiogenesis in several
types of tumor cells. 15-Deoxy-&12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand
of peroxisome proliferator-activated receptor $, has been known to induce HO-1 in some cell
lines. In the present work, we found that treatment of human breast cancer (MCF-7) cells
with nontoxic doses of 15d-PGJ2 led to concentration- and time-dependent increases in the
expression and activity of HO-1. The induction of HO-1 expression preceded the
upregulation of vascular endothelial growth factor (VEGF) in MCF-7 cells stimulated with
15d-PGJ2. The upregulation of VEGF production by 15d-PGJ2 was abrogated by the HO-1
inhibitor, ZnPP. Moreover, ZnPP decreased the in vitro capillary formation induced by 15d-
PGJ2 in human umbilical vein endothelial cells. Likewise, ZnPP treatment mitigated the
manifestation of migrative phenotype of 15d-PGJ2-treated MCF-7 cells as determined by the
wound migration assay. Nrf2, a basic-leucine zipper transcription factor, plays a key role in
regulating the antioxidant response element (ARE)-mediated expression of HO-1 and other
antioxidant enzymes. 15d-PGJ2 increased nuclear translocation and subsequent ARE binding
of Nrf2. MCF-7 cells transfected with dominant negative Nrf2 exhibited reduced expression
of HO-1 and VEGF in response to 15d-PGJ2 treatment. Taken together, these results suggest
that 15d-PGJ2-induced expression of HO-1 via the Nrf2 signaling is implicated in
angiogenesis in human breast cancer.
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