Induction of vascular endothelial growth factor by peptidyl-prolyl isomerase Pin1 in breast cancer cells

Mi Ra Kim, Hong Seok Choi, Tae Hwe Heo, Sun Wook Hwang, Keon Wook Kang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Pin1, a peptidyl-prolyl isomerase, is overexpressed in most types of cancer tissues and plays an important role in oncogenesis. We found that Pin1 increases the transcriptional activity and protein level of vascular endothelial growth factor (VEGF) in the human breast cancer cell line, MCF-7. Reporter gene analyses showed that Pin1 overexpression increased the reporter activities in cells transfected with reporters containing the VEGF gene promoter or with minimal reporters of activator protein-1 (AP-1) and hypoxia response element (HRE). VEGF reporter gene activity was significantly inhibited by either hypoxia-inducible factor-α (HIF-1α) siRNA or AP-1 decoy ODN. Moreover, the reporter activities of the VEGF promoter, AP-1 and HRE in Pin1-/- mouse embryonic fibroblast (MEF) cells were decreased compared with those in wild-type Pin1 MEF cells. These results imply that Pin1 stimulates VEGF expression by activating HIF-1α and AP-1, and suggest that Pin1 is a potential therapeutic target of angiogenesis during cancer development.

Original languageEnglish
Pages (from-to)547-553
Number of pages7
JournalBiochemical and biophysical research communications
Volume369
Issue number2
DOIs
Publication statusPublished - 2008 May 2

Keywords

  • AP-1
  • HIF-1α
  • Pin1
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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