title: Phosphatase of regenerating liver 3 (PRL-3) is overexpressed in human prostate cancer tissue and promotes growth and migration.
abstract: BACKGROUND
  PRL-3 is a phosphatase implicated in oncogenesis in multiple cancers. In some cancers, notably carcinomas, PRL-3 is also associated with inferior prognosis and increased metastatic potential. In this study we investigated the expression of PRL-3 mRNA in fresh-frozen samples from patients undergoing radical prostatectomy because of prostate cancer (PC) and the biological function of PRL-3 in prostate cancer cells.
  
  
  METHODS
  Samples from 41 radical prostatectomy specimens (168 samples in total) divided into low (Gleason score ≤ 6), intermediate (Gleason score = 7) and high (Gleason score ≥ 8) risk were analyzed with gene expression profiling and compared to normal prostate tissue. PRL-3 was identified as a gene with differential expression between healthy and cancerous tissue in these analyses. We used the prostate cancer cell lines PC3 and DU145 and a small molecular inhibitor of PRL-3 to investigate whether PRL-3 had a functional role in cancer. Relative ATP-measurement and thymidine incorporation were used to assess the effect of PRL-3 on growth of the cancer cells. We performed an in vitro scratch assay to investigate the involvement of PRL-3 in migration. Immunohistochemistry was used to identify PRL-3 protein in prostate cancer primary tumor and corresponding lymph node metastases.
  
  
  RESULTS
  Compared to normal prostate tissue, the prostate cancer tissue expressed a significantly higher level of PRL-3. We found PRL-3 to be present in both PC3 and DU145, and that inhibition of PRL-3 led to growth arrest and apoptosis in these two cell lines. Inhibition of PRL-3 led to reduced migration of the PC3 cells. Immunohistochemistry showed PRL-3 expression in both primary tumor and corresponding lymph node metastases.
  
  
  CONCLUSIONS
  PRL-3 mRNA was expressed to a greater extent in prostate cancer tissue compared to normal prostate tissue. PRL-3 protein was expressed in both prostate cancer primary tumor and corresponding lymph node metastases. The results from our in vitro assays suggest that PRL-3 promotes growth and migration in prostate cancer. In conclusion, these results imply that PRL-3 has a role in the pathogenesis of prostate cancer.
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway. estennv@stud.ntnu.no.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. estennv@stud.ntnu.no.
authors.forename: Esten N
authors.initials: EN
authors.lastname: Vandsemb
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Urology, St Olavs University Hospital, Trondheim, Norway.
authors.forename: Helena
authors.initials: H
authors.lastname: Bertilsson
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pegah
authors.initials: P
authors.lastname: Abdollahi
authors.affiliation: Department of Pathology, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Størkersen
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Pathology, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Thea Kristin
authors.initials: TK
authors.lastname: Våtsveen
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Morten Beck
authors.initials: MB
authors.lastname: Rye
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Pediatrics, St Olavs University Hospital, Trondheim, Norway.
authors.forename: Torstein Baade
authors.initials: TB
authors.lastname: Rø
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Immunology and Transfusion Medicine, St Olavs University Hospital, Trondheim, Norway.
authors.forename: Magne
authors.initials: M
authors.lastname: Børset
authors.affiliation: K. G. Jebsen Center for Myeloma Research, Norwegian University of Science and Technology, PO Box 8905, 7491, Trondheim, Norway.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Clinic of Medicine, St Olavs University Hospital, Trondheim, Norway.
authors.forename: Tobias S
authors.initials: TS
authors.lastname: Slørdahl
mesh_terms: D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D056426:Genetic Loci; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Molecular pathogenesis; Oncogenesis; PRL-3; PTP4A3; Prostate cancer