Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma.
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.
Kurose
Kyouhei
K
Department of Urology, Okayama University Graduate School of Medicine and Dentistry and Faculty of Health Sciences, Okayama, Japan.
Sakaguchi
Masakiyo
M
Nasu
Yasutomo
Y
Ebara
Shin
S
Kaku
Haruki
H
Kariyama
Reiko
R
Arao
Yujirou
Y
Miyazaki
Masahiro
M
Tsushima
Tomoyasu
T
Namba
Masayoshi
M
Kumon
Hiromi
H
Huh
Nam-Ho
NH
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
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