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.

Non-canonical dimerization of the androgen receptor and other nuclear receptors: implications for human disease

“…Carver and coworkers also observed that two genes strongly associated with cell migration, ADAMTS1 and CXCR4, were upregulated upon ERG overexpression (Carver et al 2009). Besides, overexpression of MMP9 and plexin B correlates with the presence of the fusion in samples of PCa patients and has been linked to migration and invasion of prostate cancer cells (Liu et al 2017).…”

Detection of TMPRSS2-ERG Fusion Transcript in Biopsy Specimen of Prostate Cancer Patients: A Single Centre Experience

“…Mehra et al found that TMPRSS2-ERG mRNA expression was present in 10 of 27 (37%) of hormone-refractory metastatic prostate cancer patient samples [36], and in the research of cases defined as localized prostate cancer, Liu B et al concluded that TMPRSS2-ERG fusion was positive in 28.0% (14/50) [37].The prevalence of TM-PRSS2:ERG varied according to several factors. In the meta-analysis realized by Pettersson et al in the USA, the prevalence of the fusion was 30% in a tissue from TURP samples and patients diagnosed by TURP were slightly more suggestive of associations with poor outcomes.…”

Recent advances in nanomaterials for prostate cancer detection and diagnosis

“…33 Based on this genetic alteration, the detection of post-DRE urinary TMPRSS2: ERG transcripts has been recommended as a biomarker for PCa diagnosis, known as the TMPRSS2:ERG score identified by the Clinical Laboratory Improvement Amendments (CLIA). 34,35 Besides, other genetic detective tools, including Oncotype DX Genomic Prostate Score, Prolaris Score, and Confirm MDX, have also been developed for PCa diagnosis. The Oncotype DX genomic prostate score is a quantitative assessment of RNA transcripts of 12 cancer-related genes and 5 reference genes in PCa needle specimens.…”