title: Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method.
abstract: Although chemotherapy for castration-resistant prostate cancer (CRPC) has been applied clinically in recent years, the effects are not sufficient. It is urgently necessary to develop novel therapeutics for CRPC. We previously generated Escherichia coli ampicillin secretion trap libraries of 2 prostate cancer (PCa) cell lines and normal prostate. By comparing the E. coli ampicillin secretion trap libraries of CRPC cell lines with those of androgen-sensitive PCa cell lines and normal prostate, we focused on the protein-tyrosine-phosphatase of regenerating liver 1 (PRL1) gene and analyzed its expression and biological function.
  
  
  
  The expression of PRL1 was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in clinical PCa samples. The effects of PRL1 on PCa cells were evaluated by cell growth, migration, and invasion assays. To investigate the effect of PRL1 on epidermal growth factor receptor (EGFR) signaling, PRL1 knockdown PC3 cells were examined by Western blot and immunohistochemical analyses.
  
  
  
  Quantitative reverse transcription polymerase chain reaction revealed that PRL1 was expressed much more highly in PCa than in nonneoplastic prostate samples. High expression of PRL1 detected by immunohistochemistry correlated with poor prognosis after prostatectomy and combined androgen blockade therapy. Functional analysis indicated that PRL1 stimulated cell growth, migration, and invasion in PCa cell lines. Expression EGFR and matrix metalloproteinase 9 was reduced by knockdown of PRL1 in the PC3 cell line.
  
  
  
  PRL1 regulates expression of EGFR and modulates downstream targets. PRL1 has potential as a therapeutic target in PCa including CRPC.
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan; Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Shunsuke
authors: S
authors: Shinmei
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Kazuhiro
authors: K
authors: Sentani
authors: Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Tetsutaro
authors: T
authors: Hayashi
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Naoya
authors: N
authors: Sakamoto
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan; Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Keisuke
authors: K
authors: Goto
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Htoo Zarni
authors: HZ
authors: Oo
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Yutaka
authors: Y
authors: Naito
authors: Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Jun
authors: J
authors: Teishima
authors: Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Akio
authors: A
authors: Matsubara
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors: Naohide
authors: N
authors: Oue
authors: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors: Hiroki
authors: H
authors: Kuniyasu
authors: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan. Electronic address: wyasui@hiroshima-u.ac.jp.
authors: Wataru
authors: W
authors: Yasui
mesh_terms: D000368:Aged; D000668:Ampicillin Resistance / Q000235:genetics; D000726:Androgen Antagonists / Q000627:therapeutic use; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011468:Prostatectomy / Q000379:methods; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D066246:ErbB Receptors; C490198:PTP4A1 protein, human; D017027:Protein Tyrosine Phosphatases; D020780:Matrix Metalloproteinase 9
keywords: CRPC; EGFR; Immunohistochemistry; MMP9; PTP4A1; Prognosis