title: Identification of TMPRSS2-ERG mechanisms in prostate cancer invasiveness: Involvement of MMP-9 and plexin B1.
abstract: The relationship of TMPRSS2-ERG fusion gene with matrix metalloproteinase-9 (MMP-9) and PLXNB1 (plexin B1) in regulation of prostate cancer (PCa) aggressiveness was investigated. Fluorescence in situ hybridization (FISH) assays, qRT-PCR and western blot analysis were employed to detect the expression of TMPRSS2-ERG fusion gene, ERG, MMP-9 and PLXNB1 of 135 human tissues, which included 55 metastatic PCa cases, 50 localized PCa cases and 30 BPH cases. Then using siRNA (anti-ERG, MMP-9 and PLXNB1, respectively) downregulation of the target gene of VCaP and PC-3 cells, MTT and Transwell were performed. The results showed that the positive rate of TMPRSS2-ERG fusion was 38.1% (40/105) in total PCa samples, 47.3% (26/55) of metastatic PCa, 28.0% (14/50) of localized PCa, while 0.0% (0/30) in BPH samples. The mRNA and protein expression of ERG, MMP-9 and PLXNB1 were higher in metastatic PCa (P<0.0001), and the mRNA expression of the three genes were positively correlated with TMPRSS2-ERG fusionin PCa group (P<0.0001). siRNA transfected PCa cells can effectively downregulate the target gene expression, and we identified that MMP-9 and PLXNB1 expression were all regulated by TMPRSS2-ERG fusion gene. While only PLXNB1 contributed to TMPRSS2-ERG mediated enhancements of VCaP cell migration and invasion. The results demonstrated that PLXNB1, but not MMP-9, was the target gene directly related to TMPRSS2-ERG in PCa cell migration and invasion.
authors.affiliation: Department of Urology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Bide
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Urology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Urology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Urology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Department of Urology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Ding
mesh_terms: D000368:Aged; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; C492119:PLXNB1 protein, human; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C515553:TMPRSS2-ERG fusion protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9