15‐deoxy‐Δ12,14‐prostaglandin j2 upregulates vegf expression via nrf2 and heme oxygenase‐1 in human breast cancer cells

Eun Hee Kim, Su Jung Kim, Hye Kyung Na, Wonshik Han, Nam Jung Kim, Young Ger Suh, Young Joon Surh

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

There is a plethora of evidence to support that inflammation is causally linked to carcino-genesis. 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‐de-oxy‐Δ12,14‐prostaglandin J2 (15d‐PGJ2), 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‐PGJ2 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‐PGJ2 during inflammatory response activate VEGF expression through NRF2‐driven induction of HO‐1 in human breast cancer cells, proposing a novel mechanism underlying the on-cogenic function of 15d‐PGJ2.

Original languageEnglish
Article number526
Pages (from-to)1-24
Number of pages24
JournalCells
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords

  • 15‐Deoxy‐Δ‐prostaglandin J2
  • Angiogenesis
  • Breast cancer
  • Heme oxygenase‐1
  • MCF‐ 7 cells
  • NRF2
  • VEGF

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