期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 369, 期 2, 页码 547-553出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.02.045
关键词
AP-1; HIF-1 alpha; Pin1; VEGF
资金
- National Research Foundation of Korea [핵C6A3404] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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-alpha (HIF-1 alpha) 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-1 alpha and AP-1, and suggest that Pin1 is a potential therapeutic target of angiogenesis during cancer development. (C) 2008 Published by Elsevier Inc.
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