Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells

BMC Cancer

Jennifer Munkley¹  Nicholas P Lafferty¹  Gabriela Kalna²  Craig N Robson⁴  Hing Y Leung³  Prabhakar Rajan³  David J Elliott¹ 

[1] Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne NE1 3BZ, UK

[2] Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK

[3] Institute of Cancer Sciences, University of Glasgow, Glasgow G12 8QQ, UK

[4] Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK

关键词: Prostate cancer;    Androgens;    MAP Kinase;    RAS/ERK1/2;    PTPRR;   

Others  :  1106751
DOI  :  10.1186/s12885-015-1012-8

 received in 2014-05-27, accepted in 2015-01-06,  发布年份 2015

【 摘 要 】

Background

Androgens drive the onset and progression of prostate cancer (PCa) via androgen receptor (AR) signalling. The principal treatment for PCa is androgen deprivation therapy, although the majority of patients eventually develop a lethal castrate-resistant form of the disease, where despite low serum testosterone levels AR signalling persists. Advanced PCa often has hyper-activated RAS/ERK1/2 signalling thought to be due to loss of function of key negative regulators of the pathway, the details of which are not fully understood.

Methods

We recently carried out a genome-wide study and identified a subset of 226 novel androgen-regulated genes (PLOS ONE 6:e29088, 2011). In this study we have meta-analysed this dataset with genes and pathways frequently mutated in PCa to identify androgen-responsive regulators of the RAS/ERK1/2 pathway.

Results

We find the PTGER4 and TSPYL2 genes are up-regulated by androgen stimulation and the ADCY1, OPKR1, TRIB1, SPRY1 and PTPRR are down-regulated by androgens. Further characterisation of PTPRR protein in LNCaP cells revealed it is an early and direct target of the androgen receptor which negatively regulates the RAS/ERK1/2 pathway and reduces cell proliferation in response to androgens.

Conclusion

Our data suggest that loss of PTPRR in clinical PCa is one factor that might contribute to activation of the RAS/ERK1/2 pathway.

【 授权许可】

   
2015 Munkley et al.; licensee BioMed Central.

【 图 表 】

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