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Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells

Authors: Turid Eide, Håkon Ramberg, Carlotta Glackin, Donald Tindall, Kristin Austlid Taskén

Published in: Cancer Cell International | Issue 1/2013

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Abstract

Background

TWIST1 plays a key role in EMT-mediated tumor invasion and metastasis. Since bone metastasis is a hallmark of advanced prostate cancer and is detected in at least 85% of patients who die of this disease, it is of great importance to understand the regulation of the cellular signaling pathways involved in the metastatic process.

Methods

Prostatic cell lines were analyzed using real time RT-PCR, chromatin immunoprecipitations (ChIP) and transfection of siRNA’s and reporter constructs.

Results

We report in this paper that TWIST1 is an androgen-regulated gene under tight regulation of NKX3-1. Androgens repress the expression of TWIST1 via NKX3-1, which is a prostate–specific tumor suppressor that is down-regulated in the majority of metastatic prostate tumors. We show that NKX3-1 binds to the TWIST1 promoter and that NKX3-1 over-expression reduces the activity of a TWIST1 promoter reporter construct, whereas NKX3-1 siRNA up-regulates endogenous TWIST1 mRNA in prostate cancer cells.

Conclusion

Our finding that NKX3-1 represses TWIST1 expression emphasizes the functional importance of NKX3-1 in regulating TWIST1 expression during prostate cancer progression to metastatic disease.
Appendix
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Metadata
Title
TWIST1, A novel androgen-regulated gene, is a target for NKX3-1 in prostate cancer cells
Authors
Turid Eide
Håkon Ramberg
Carlotta Glackin
Donald Tindall
Kristin Austlid Taskén
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-4

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