ETS variant 1 regulates matrix metalloproteinase-7 transcription in             LNCaP prostate cancer cells.
Prostate cancer is characterized by the recurrent translocation of ETS transcription             factors, including ETS variant 1 (ETV1) [also known as ETS-related 81 (ER81)].             Transgenic ETV1 mice develop prostatic intraepithelial neoplasia, yet the mechanisms             by which ETV1 exerts its deleterious function remain largely unexplored. In this             study, we demonstrated that ETV1 is capable of binding to the matrix metalloproteinase-7             (MMP-7) gene promoter both in vitro and in vivo. ETV1 stimulated the activity             of the MMP-7 promoter, which was suppressed upon mutation of two ETV1 binding             sites located within 200 base pairs upstream of the MMP-7 transcription start             site. ETV1 overexpression in human LNCaP prostate cancer cells induced endogenous             MMP-7 gene transcription, whereas ETV1 downregulation had the opposite effect.             While MMP-7 overexpression did not influence LNCaP cell proliferation, it increased             cell migration, which may be important during later stages of tumorigenesis. Finally,             MMP-7 mRNA was significantly overexpressed in human prostate tumors compared to             normal tissue. Together, these results showed that MMP-7 is a bona fide ETV1 target             gene, implicating that MMP-7 upregulation is partially responsible for the oncogenic             effects of ETV1 in the prostate.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Sook
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Shin
Sangphil
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Oh
Seayoon
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An
Ralf
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Janknecht
D017209:Apoptosis; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D008156:Luciferases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7