Induction of vascular endothelial growth factor by peptidyl-prolyl isomerase Pin1 in breast cancer cells.
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-1alpha) 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-1alpha and AP-1, and suggest that Pin1 is a potential therapeutic target of angiogenesis during cancer development.
Kim
Mi Ra
MR
BK21 Project Team, Chosun University, Gwangju 501-759, Republic of Korea.
Choi
Hong Seok
HS
Heo
Tae-Hwe
TH
Hwang
Sun Wook
SW
Kang
Keon Wook
KW
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D018808:Transcription Factor AP-1; D042461:Vascular Endothelial Growth Factor A; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse