title: Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma.
abstract: OBJECTIVE
  We examined the expression of REIC/Dkk-3, a possible candidate for a tumor suppressor gene, in human renal clear cell carcinoma (RCCC) cell lines and sporadic RCCC surgical specimens.
  
  
  METHODS
  Human RCCC cell lines (Caki-1, Caki-2, ACHN and KPK-1) and several control cell lines were used to examine the expression of REIC/Dkk-3 mRNA and characterize a newly raised antibody specific for REIC/Dkk-3 protein. Pairs of cancerous and adjacent noncancerous tissues were obtained from 20 patients with RCCC. Of them 17 and 7 cases were analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction, and by Western blot analysis and/or immunohistochemical analysis, respectively.
  
  
  RESULTS
  The decreased expression of REIC/Dkk-3 mRNA and protein in human RCCC cell lines, and the specificity of the new antibody were confirmed. In a real-time quantitative reverse transcriptase-polymerase chain reaction study using 17 pairs of RCCC and adjacent normal tissues REIC/Dkk-3 mRNA levels were significantly decreased in carcinoma tissues (by 25% to approximately 95% in 15 pairs). Western blot analysis and immunohistochemistry revealed a significant decrease in REIC/Dkk-3 protein levels in 6 of the 7 and 13 of the 14 RCCC cases analyzed, respectively.
  
  
  CONCLUSIONS
  The decrease in REIC/Dkk-3 mRNA and protein levels was observed irrespective of tumor grade and stage, indicating the involvement of REIC/Dkk-3 in an initial step of malignant conversion. Consequently REIC/Dkk-3 could be a new molecular target for therapeutic measures against RCCC.
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine and Dentistry and Faculty of Health Sciences, Okayama, Japan.
authors.forename: Kyouhei
authors.initials: K
authors.lastname: Kurose
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Shin
authors.initials: S
authors.lastname: Ebara
authors.forename: Haruki
authors.initials: H
authors.lastname: Kaku
authors.forename: Reiko
authors.initials: R
authors.lastname: Kariyama
authors.forename: Yujirou
authors.initials: Y
authors.lastname: Arao
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Tsushima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Namba
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000912:Antibodies, Neoplasm / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics; D018925:Chemokines; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007680:Kidney Neoplasms / Q000276:immunology / Q000378:metabolism*; D011506:Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000912:Antibodies, Neoplasm; D002352:Carrier Proteins; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins