title: VEGF promotes the transcription of the human PRL-3 gene in HUVEC through transcription factor MEF2C.
abstract: Phosphatase of regenerating liver 3 (PRL-3) is known to be overexpressed in many tumors, and its transcript level is high in the vasculature and endothelial cells of malignant tumor tissue. However, the mechanism(s) underlying its enhanced expression and its function in endothelial cells remain unknown. Here, we report that vascular endothelial growth factor (VEGF) can induce PRL-3 transcription in human umbilical vein endothelial cells (HUVEC). An analysis of its 5'UTR revealed that PRL-3 transcription is initiated from two distinct sites, which results in the formation of the two transcripts, PRL-3-iso1 and PRL-3-iso2, but only the latter is up-regulated in HUVEC by VEGF. The PRL-3-iso2 promoter region includes two functional MEF2 (myocyte enhancer factor2) binding sites. The over-expression of the constitutively active form of MEF2C promotes the abundance of the PRL-3-iso2 transcript in a number of human cell lines. The siRNA-induced knockdown of MEF2C abolished the stimulative effect of VEGF on PRL-3 transcript in HUVEC, indicating that the VEGF-induced promotion of PRL-3 expression requires the presence of MEF2C. Finally, blocking PRL-3 activity or expression suppresses tube formation by HUVEC. We suggest that PRL-3 functions downstream of the VEGF/MEF2C pathway in endothelial cells and may play an important role in tumor angiogenesis.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Xu
authors.forename: Shaoxian
authors.initials: S
authors.lastname: Cao
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism / Q000502:physiology*; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D020121:5' Untranslated Regions; D017931:DNA Primers; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D018006:Myogenic Regulatory Factors; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
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