Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma

Kyouhei Kurose, Masakiyo Sakaguchi, Yasutomo Nasu, Shin Ebara, Haruki Kaku, Reiko Kariyama, Yujirou Arao, Masahiro Miyazaki, Tomoyasu Tsushima, Masayoshi Namba, Hiromi Kumon, Nam Ho Huh

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

Abstract

Purpose: 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. Materials and 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.

Original languageEnglish
Pages (from-to)1314-1318
Number of pages5
JournalJournal of Urology
Volume171
Issue number3
DOIs
Publication statusPublished - Mar 2004

Keywords

  • Adenocarcinoma, clear cell
  • Carcinoma, renal cell
  • Genes, tumor suppressor
  • Kidney

ASJC Scopus subject areas

  • Urology

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