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Updated: May 15, 2026
MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR (qPCR)
Published on: May 16, 2012
Identification of TDRD1 as a direct target gene of ERG in primary prostate cancer
Joost L Boormans1, Hanneke Korsten, Angelique J C Ziel-van der Made
1Department of Urology Erasmus Medical Centre, Rotterdam, The Netherlands. j.boormans@erasmusmc.nl
Abstract:
Molecular classification of ERG-rearranged prostate cancer clarifies the role of TMPRSS2-ERG in the development and progression of prostate cancer. The objective of our study was to identify direct ERG target genes in ERG-rearranged prostate cancer. Two independent cohorts of primary prostate cancer (Cohort A, n=48; Cohort B, n=31), a cohort of late-stage prostate cancer (n=51) and expression array data of a cohort of primary prostate tumors from a different institute (n=128) were analyzed for expression of genes that were coexpressed with ERG overexpression. By genome-wide expression analysis and Q-RT-PCR it was shown that the gene Tudor domain containing 1 (TDRD1) was by far the strongest correlated gene with ERG overexpression in both Cohort A and B. Expression array analysis of the patient cohort from a different institute showed a large overlap in genes that were positively correlated with ERG overexpression, including TDRD1. In late-stage prostate cancer, TDRD1 was also coexpressed with ERG overexpression, although a proportion of ERG-negative late-stage samples expressed TDRD1. TDRD1 expression was not associated with ETV1 overexpression. In the prostate cancer cell line VCaP, downregulation of ERG by shRNA lead to a lower expression level of TDRD1 and resulted in a decreased activity of the TDRD1 promoter. By mutation analysis we identified a functional ERG binding site in the TDRD1 promoter. Our findings show TDRD1 as the first identified upregulated direct ERG target gene that is strongly associated with ERG overexpression in primary prostate cancer.
Insights
Researchers identified the Tudor domain containing 1 (TDRD1) gene as the first direct target of ERG overexpression in prostate cancer. This finding clarifies the role of TMPRSS2-ERG in cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer molecular classification is crucial for understanding disease development.
- TMPRSS2-ERG fusion is a key driver in a significant subset of prostate cancers.
- Identifying direct ERG target genes is essential for elucidating ERG's role.
Purpose of the Study:
- To identify direct ERG target genes in ERG-rearranged prostate cancer.
- To investigate the relationship between ERG overexpression and gene expression patterns.
- To validate potential target genes in various prostate cancer cohorts and cell lines.
Main Methods:
- Genome-wide expression analysis and quantitative reverse transcription PCR (Q-RT-PCR) on independent prostate cancer cohorts.
- Analysis of gene expression data from multiple patient cohorts and a prostate cancer cell line (VCaP).
- RNA interference (shRNA) to downregulate ERG, promoter activity assays, and mutation analysis to identify ERG binding sites.
Main Results:
- Tudor domain containing 1 (TDRD1) was identified as the strongest gene correlated with ERG overexpression across multiple cohorts.
- TDRD1 was coexpressed with ERG in late-stage prostate cancer, though also present in some ERG-negative samples.
- ERG downregulation reduced TDRD1 expression and promoter activity, with a functional ERG binding site identified in the TDRD1 promoter.
Conclusions:
- TDRD1 is the first identified upregulated direct ERG target gene in prostate cancer.
- TDRD1 expression is strongly associated with ERG overexpression in primary prostate cancer.
- These findings enhance the understanding of ERG's regulatory network in prostate cancer pathogenesis.
