ETS variant 1 regulates matrix metalloproteinase-7 transcription in LNCaP prostate cancer cells

Prostate cancer is characterized by the recurrent translocation of ETS transcriptionfactors, including ETS variant 1 (ETV1) [also known as ETS-related 81 (ER81)].Transgenic ETV1 mice develop prostatic intraepithelial neoplasia, yet the mechanismsby which ETV1 exerts its deleterious function remain largely unexplored. In thisstudy, 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 activityof the MMP-7 promoter, which was suppressed upon mutation of two ETV1 bindingsites located within 200 base pairs upstream of the MMP-7 transcription startsite. ETV1 overexpression in human LNCaP prostate cancer cells induced endogenousMMP-7 gene transcription, whereas ETV1 downregulation had the opposite effect.While MMP-7 overexpression did not influence LNCaP cell proliferation, it increasedcell migration, which may be important during later stages of tumorigenesis. Finally,MMP-7 mRNA was significantly overexpressed in human prostate tumors compared tonormal tissue. Together, these results showed that MMP-7 is a bona fide ETV1 targetgene, implicating that MMP-7 upregulation is partially responsible for the oncogeniceffects of ETV1 in the prostate.