Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Shaikhibrahim, Zaki; Langer, Berit; Lindstrot, Andreas; Florin, Alexandra; Bosserhoff, Anja‐Katrin; Buettner, Reinhard; Wernert, Nicolas

doi:10.3892/or.2011.1156

Cited by 5 publications

(1 citation statement)

References 24 publications

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“…The rationale behind choosing the latter ETS members was as follows: ETS-1 is the prototype of the ETS family and has been reported to be overexpressed in latent as well as clinically manifest PCa and a strong expression of ETS-1 has been associated with poor tumor differentiation (25). As shown in a previous study of our, the blockade of ETS-1 in PCa cell lines results in a decrease in cell migration (11) and has a major effect upon genes involved in the metastatic cascade (12). As ETS-1 and ETS-2 have been reported to play redundant roles during embryonic development (17), combined with reports that ETS-2 is associated with in vitro synthesized ETS-1 (26) and that ETS-2 interacts with ERG in vivo demonstrated by the two-hybrid system (26), we decided to investigate ETS-2 as well.…”

Section: Discussionmentioning

confidence: 57%

ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer

Shaikhibrahim

Ochsenfahrt

Fuchs

et al. 2012

International Journal of Molecular Medicine

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The erythroblast transformation-specific (ETS) family of transcription factors plays important roles in both physiological and pathological conditions. Even though many studies have focused on single ETS factors within a single tissue and within the context of specific promoters, the functional impact of multiple ETS members present within a specific cell type has not yet been investigated, especially in prostate cancer (PCa). As the most prominent gene rearrangement in PCa leads to the overexpression of the ETS-related gene (ERG), the aim of this study was to investigate whether ERG is part of a complex integrated transcriptional network that involves other ETS factors. More specifically, as the ETS family consists of 27 members, we focused our efforts initially on investigating whether ERG is associated with the three family members, ETS-1, ETS-2 and ETS variant gene-4 (ETV-4), in PCa as a proof of principle. Using western blot analysis, we show that ERG, ETS-1, ETS-2 and ETV-4 are expressed in PC3 cell nuclear extracts and in protein lysates prepared from human PCa prostatectomy specimens. Immunoprecipitations using an anti-ERG antibody were used with PC3 cell nuclear extracts as well as with a pooled protein lysate sample prepared from the PCa tissue samples of five patients. Importantly, our results revealed that ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in PC3 cell nuclear extracts and PCa tissue protein lysates. Our findings strongly support the notion that ERG is part of a complex integrated transcriptional network that involves other ETS factors, which are likely to cooperate or influence the activity of ERG in PCa. The functional impact of multiple ETS factors being associated with ERG in PCa requires further study, as it may provide insights into the mechanism by which ERG exerts its influence in PCa and may subsequently contribute to our understanding of the molecular basis of PCa.

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Section: Discussionmentioning

confidence: 57%

ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer

Shaikhibrahim

Ochsenfahrt

Fuchs

et al. 2012

International Journal of Molecular Medicine

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XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin‐mediated Rho‐GDIβ mRNA stability

Jin

et al. 2017

Intl Journal of Cancer

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Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIβ expression and reduced cancer cell invasion, whereas RhoGDIβ expression was attenuated in BBN-treated urothelium of RING-deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIβ mRNA by its positively regulating nucleolin mRNA stability via Erks-dependent manner. Moreover, ectopic expression of GFP-RhoGDIβ in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP-regulated Erks/nucleolin/RhoGDIβ axis promoted BC invasion and lung metastasis.

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Micro-RNA-204 Participates in TMPRSS2/ERG Regulation and Androgen Receptor Reprogramming in Prostate Cancer

et al. 2017

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Cancer progression is driven by genome instability incurred rearrangements such as transmembrane protease, serine 2 (TMPRSS2)/v-ets erythroblastosis virus E26 oncogene (ERG) that could possibly turn some of the tumor suppressor micro-RNAs into pro-oncogenic ones. Previously, we found dualistic miR-204 effects, acting either as a tumor suppressor or as an oncomiR in ERG fusion-dependent manner. Here, we provided further evidence for an important role of miR-204 for TMPRSS2/ERG and androgen receptor (AR) signaling modulation and fine tuning that prevents TMPRSS2/ERG overexpression in prostate cancer. Based on proximity-based ligation assay, we designed a novel method for detection of TMPRSS2/ERG protein products. We found that miR-204 is TMPRSS2/ERG oncofusion negative regulator, and this was mediated by DNA methylation of TMPRSS2 promoter. Transcriptional factors runt-related transcription factor 2 (RUNX2) and ETS proto-oncogene 1 (ETS1) were positive regulators of TMPRSS2/ERG expression and promoter hypo-methylation. Clustering of patients' sera for fusion protein, transcript expression, and wild-type ERG transcript isoforms, demonstrated not all patients harboring fusion transcripts had fusion protein products, and only few fusion positive ones exhibited increased wild-type ERG transcripts. miR-204 upregulated AR through direct promoter hypo-methylation, potentiated by the presence of ERG fusion and RUNX2 and ETS1. Proteomics studies provided evidence that miR-204 has dualistic role in AR cancer-related reprogramming, promoting prostate cancer-related androgen-responsive genes and AR target genes, as well as AR co-regulatory molecules. miR-204 methylation regulation was supported by changes in molecules responsible for chromatin remodeling, DNA methylation, and its regulation. In summary, miR-204 is a mild regulator of the AR function during the phase of preserved AR sensitivity as the latter one is required for ERG-fusion translocation.

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Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Cited by 5 publications

References 24 publications

ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer

ERG is specifically associated with ETS-2 and ETV-4, but not with ETS-1, in prostate cancer

XIAP overexpression promotes bladder cancer invasion in vitro and lung metastasis in vivo via enhancing nucleolin‐mediated Rho‐GDIβ mRNA stability

Micro-RNA-204 Participates in TMPRSS2/ERG Regulation and Androgen Receptor Reprogramming in Prostate Cancer

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