title: Receptor-like protein tyrosine phosphatase κ negatively regulates the apoptosis of prostate cancer cells via the JNK pathway.
abstract: Receptor-like protein tyrosine phosphatase κ (PTPRK) has been indicated as a putative tumour suppressor in primary central nervous system lymphomas and colorectal cancer. The present study investigated the expression of PTPRK in prostate cancer and the biological impact of PTPRK on prostate cancer cells. The expression of the PTPRK protein and transcript in prostate cancer was examined using IHC and PCR. Knockdown of PTPRK in prostate cancer cells was performed using a specific anti-PTPRK transgene. The impact of PTPRK knockdown on prostate cancer cells was evaluated using in vitro cell models and the apoptosis was analysed using flow cytometry. PTPRK expression was increased in prostate cancer tissues and knockdown of PTPRK in PC-3 cells suppressed the in vitro cell growth in which an increased apoptotic population was seen. Accompanied with the knockdown of PTPRK, increased expression of caspase-3, caspase-8 and p53, and a decreased ID1 expression were evident in the cells. Furthermore, an increased tyrosine phosphorylated c-Jun N-terminal kinase (JNK) was seen in the PTPRK knockdown cells. The effect on apoptosis was diminished by a JNK inhibitor. In conclusion, PTPRK knockdown resulted in increased apoptosis leading to the inhibition of in vitro growth of prostate cancer cells. PTPRK is a key factor in coordinating apoptosis via the regulation of MAPK pathways, in particular the JNK pathway in prostate cancer cells.
authors.affiliation: Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Ping-Hui
authors.initials: PH
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D006801:Humans; D007124:Immunoenzyme Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048031:JNK Mitogen-Activated Protein Kinases; C489852:PTPRK protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2