title: Androgen-regulation of the protein tyrosine phosphatase PTPRR activates ERK1/2 signalling in prostate cancer cells.
abstract: 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.
  
  
  CONCLUSIONS
  Our data suggest that loss of PTPRR in clinical PCa is one factor that might contribute to activation of the RAS/ERK1/2 pathway.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK. jennifer.munkley@ncl.ac.uk.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Munkley
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK. n.p.lafferty@gmail.com.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Lafferty
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. g.kalna@beatson.gla.ac.uk.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kalna
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK. c.n.robson@ncl.ac.uk.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Robson
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. Hing.Leung@glasgow.ac.uk.|Institute of Cancer Sciences, University of Glasgow, Glasgow, G12 8QQ, UK. Hing.Leung@glasgow.ac.uk.
authors.forename: Hing Y
authors.initials: HY
authors.lastname: Leung
authors.affiliation: Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. Prabhakar.Rajan@glasgow.ac.uk.|Institute of Cancer Sciences, University of Glasgow, Glasgow, G12 8QQ, UK. Prabhakar.Rajan@glasgow.ac.uk.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Rajan
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 3BZ, UK. david.elliott@ncl.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elliott
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7 / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000728:Androgens; D011944:Receptors, Androgen; C513469:PTPRR protein, human; D054634:Receptor-Like Protein Tyrosine Phosphatases, Class 7