Journal
CANCER RESEARCH
Volume 73, Issue 14, Pages 4533-4547Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-4537
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Funding
- Oncosuisse [KFS-01913-08, KFS-02573-02-2010]
- Swiss National Science Foundation [FNS-31003A-118113]
- Ticino Foundation for Cancer Research, Fondazione Virginia Boeger and Fondazione Fidinam
- Compagnia di San Paolo, Torino, Italy
- AIRC
- Associazione Italiana per la Ricerca sul Cancro [MFAG-11742]
- SNSF International Short Visit Fellowship
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Chromosomal translocations leading to deregulated expression of ETS transcription factors are frequent in prostate tumors. Here, we report a novel mechanism leading to oncogenic activation of the ETS factor ESE1/ELF3 in prostate tumors. ESE1/ELF3 was overexpressed in human primary and metastatic tumors. It mediated transforming phenotypes in vitro and in vivo and induced an inflammatory transcriptome with changes in relevant oncogenic pathways. ESE1/ELF3 was induced by interleukin (IL)-1 beta through NF-kappa B and was a crucial mediator of the phenotypic and transcriptional changes induced by IL-1 beta in prostate cancer cells. This linkage was mediated by interaction of ESE1/ELF3 with the NF-kappa B subunits p65 and p50, acting by enhancing their nuclear translocation and transcriptional activity and by inducing p50 transcription. Supporting these findings, gene expression profiling revealed an enrichment of NF-kappa B effector functions in prostate cancer cells or tumors expressing high levels of ESE1/ELF3. We observed concordant upregulation of ESE1/ELF3 and NF-kappa B in human prostate tumors that was associated with adverse prognosis. Collectively, our results define an important new mechanistic link between inflammatory signaling and the progression of prostate cancer.
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