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

Cancer Cell International

Kristin Austlid Taskén²  Donald Tindall³  Carlotta Glackin⁴  Håkon Ramberg¹  Turid Eide¹ 

[1] Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway;Faculty of Medicine, University of Oslo, Oslo, Norway;Department of Urology, Mayo Clinic and Foundation, Rochester, 55905, MN, USA;Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, 91010-3011, CA, USA

关键词: NKX3-1;    TWIST1;    LNCaP cells;    Prostate cancer;   

Others  :  794491
DOI  :  10.1186/1475-2867-13-4

 received in 2012-08-16, accepted in 2013-01-29,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Eide et al.; licensee BioMed Central Ltd.

【 图 表 】

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