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

摘要: Background: Androgens drive the onset and progression of prostate cancer (PCa) via androgen receptor (AR) signalling. The principal treatment for PCa is deprivation therapy, although majority patients eventually develop a lethal castrate-resistant form disease, where despite low serum testosterone levels AR signalling persists. Advanced often has hyper-activated RAS/ERK1/2 thought to be due loss function key negative regulators pathway, details which are not fully understood. Methods: We recently carried out genome-wide study identified subset 226 novel androgen-regulated genes (PLOS ONE 6:e29088, 2011). In this we have meta-analysed dataset with pathways frequently mutated in identify androgen-responsive pathway. Results: find PTGER4 TSPYL2 up-regulated by stimulation ADCY1, OPKR1, TRIB1, SPRY1 PTPRR down-regulated androgens. Further characterisation protein LNCaP cells revealed it an early direct target negatively regulates pathway reduces cell proliferation response Conclusion: Our data suggest that clinical one factor might contribute activation