title: Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer.
abstract: BACKGROUND
  Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer.
  
  
  METHODS
  ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19.
  
  
  RESULTS
  Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration.
  
  
  CONCLUSIONS
  Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer.
authors.affiliation: School of Health Sciences and Institute of Health Science Research, The University of Notre Dame Australia, Fremantle Campus, Australia. gerard.hoyne@nd.edu.au.
authors.forename: Gerard
authors.initials: G
authors.lastname: Hoyne
authors.affiliation: Royal Perth Hospital, Perth, Australia. caroline.rudnicka@uwa.edu.au.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rudnicka
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA. qxsang@chem.fsu.edu.
authors.forename: Qing-Xiang
authors.initials: QX
authors.lastname: Sang
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, USA. dru.roycik@gmail.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Roycik
authors.affiliation: School of Health Sciences and Institute of Health Science Research, The University of Notre Dame Australia, Fremantle Campus, Australia. sarahhowarth90@gmail.com.|Harry Perkins Institute of Medical Research and the Centre for Medical Research, The University of Western Australia, Perth, Australia. sarahhowarth90@gmail.com.
authors.forename: Sarah
authors.initials: S
authors.lastname: Howarth
authors.affiliation: Harry Perkins Institute of Medical Research and the Centre for Medical Research, The University of Western Australia, Perth, Australia. peter.leedman@perkins.uwa.edu.au.|School of Medicine and Pharmacology - Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia. peter.leedman@perkins.uwa.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Leedman
authors.affiliation: School of Medicine and Pharmacology - Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia. markus.schlaich@uwa.edu.au.
authors.forename: Markus
authors.initials: M
authors.lastname: Schlaich
authors.affiliation: Harry Perkins Institute of Medical Research and the Centre for Medical Research, The University of Western Australia, Perth, Australia. patrick.candy@perkins.uwa.edu.au.
authors.forename: Patrick
authors.initials: P
authors.lastname: Candy
authors.affiliation: Harry Perkins Institute of Medical Research and the Centre for Medical Research, The University of Western Australia, Perth, Australia. vance.matthews@uwa.edu.au.|School of Medicine and Pharmacology - Royal Perth Hospital Unit, The University of Western Australia, Perth, Australia. vance.matthews@uwa.edu.au.|School of Medicine and Pharmacology- Royal Perth Hospital Unit, Level 3, Medical Research Foundation Building, Rear 50 Murray Street, Perth, WA, 6000, Australia. vance.matthews@uwa.edu.au.
authors.forename: Vance
authors.initials: V
authors.lastname: Matthews
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; C411902:ADAM19 protein, human