PMID- 33801351
OWN - NLM
STAT- MEDLINE
DCOM- 20211119
LR  - 20211119
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 10
IP  - 3
DP  - 2021 Mar 2
TI  - 15-Deoxy-Delta(12,14)-prostaglandin J(2) Upregulates VEGF Expression via NRF2 and 
      Heme Oxygenase-1 in Human Breast Cancer Cells.
LID - 10.3390/cells10030526 [doi]
LID - 526
AB  - There is a plethora of evidence to support that inflammation is causally linked 
      to carcinogenesis. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme in the 
      biosynthesis of prostaglandins, is inappropriately overexpressed in various 
      cancers and hence recognized as one of the hallmarks of chronic 
      inflammation-associated malignancies. However, the mechanistic role of COX-2 as a 
      link between inflammation and cancer remains largely undefined. In this study, we 
      found that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), one of the final 
      products of COX-2, induced upregulation of vascular endothelial growth factor 
      (VEGF) and capillary formation and migration through nuclear factor erythroid 
      2-related factor 2 (NRF2)-dependent heme oxygenase-1 (HO-1) induction in MCF-7 
      cells. Analysis of the publicly available TCGA data set showed that high mRNA 
      levels of both COX-2 and NRF2 correlated with the poor clinical outcomes in 
      breast cancer patients. Moreover, human tissue analysis showed that the levels of 
      15d-PGJ(2) as well the expression of COX-2, NRF2, and HO-1 were found to be 
      increased in human breast cancer tissues. In conclusion, the elevated levels of 
      15d-PGJ(2) during inflammatory response activate VEGF expression through 
      NRF2-driven induction of HO-1 in human breast cancer cells, proposing a novel 
      mechanism underlying the oncogenic function of 15d-PGJ(2).
FAU - Kim, Eun-Hee
AU  - Kim EH
AUID- ORCID: 0000-0002-8523-0440
AD  - College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 
      Seongnam 13488, Korea.
FAU - Kim, Su-Jung
AU  - Kim SJ
AD  - Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul 
      National University, Seoul 08826, Korea.
FAU - Na, Hye-Kyung
AU  - Na HK
AD  - Department of Food Science and Biotechnology, College of Knowledge-Based Services 
      Engineering, Sungshin Women's University, Seoul 01133, Korea.
FAU - Han, Wonshik
AU  - Han W
AD  - Cancer Research Institute, Seoul National University, Seoul 03080, Korea.
AD  - Department of Surgery, Seoul National University College of Medicine, Seoul 
      03080, Korea.
FAU - Kim, Nam-Jung
AU  - Kim NJ
AD  - College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.
FAU - Suh, Young-Ger
AU  - Suh YG
AD  - College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 
      Seongnam 13488, Korea.
FAU - Surh, Young-Joon
AU  - Surh YJ
AD  - Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul 
      National University, Seoul 08826, Korea.
AD  - Cancer Research Institute, Seoul National University, Seoul 03080, Korea.
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul 08826, 
      Korea.
LA  - eng
GR  - BK21 FOUR Program (5120200513755)/National Research Foundation of Korea/
GR  - GCRC Grant (No. 2011-0030001)/National Research Foundation of Korea/
GR  - Basic Science Research Program grant (No. 2020R1F1A1076477)/National Research 
      Foundation of Korea/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210302
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Prostaglandins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Cyclooxygenase 2/*adverse effects
MH  - Female
MH  - Heme Oxygenase-1/*metabolism
MH  - Humans
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Prostaglandins/*metabolism
MH  - Transfection
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/*metabolism
PMC - PMC8002112
OTO - NOTNLM
OT  - 15-Deoxy-Delta12,14-prostaglandin J2
OT  - MCF-7 cells
OT  - NRF2
OT  - VEGF
OT  - angiogenesis
OT  - breast cancer
OT  - heme oxygenase-1
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/11/20 06:00
PMCR- 2021/03/02
CRDT- 2021/04/03 01:08
PHST- 2021/01/02 00:00 [received]
PHST- 2021/02/23 00:00 [revised]
PHST- 2021/02/25 00:00 [accepted]
PHST- 2021/04/03 01:08 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/11/20 06:00 [medline]
PHST- 2021/03/02 00:00 [pmc-release]
AID - cells10030526 [pii]
AID - cells-10-00526 [pii]
AID - 10.3390/cells10030526 [doi]
PST - epublish
SO  - Cells. 2021 Mar 2;10(3):526. doi: 10.3390/cells10030526.