TY - JOUR
T1 - Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma
AU - Kurose, Kyouhei
AU - Sakaguchi, Masakiyo
AU - Nasu, Yasutomo
AU - Ebara, Shin
AU - Kaku, Haruki
AU - Kariyama, Reiko
AU - Arao, Yujirou
AU - Miyazaki, Masahiro
AU - Tsushima, Tomoyasu
AU - Namba, Masayoshi
AU - Kumon, Hiromi
AU - Huh, Nam Ho
N1 - Funding Information:
Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and Japan Society for the Promotion of Science.
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
KW - Adenocarcinoma, clear cell
KW - Carcinoma, renal cell
KW - Genes, tumor suppressor
KW - Kidney
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U2 - 10.1097/01.ju.0000101047.64379.d4
DO - 10.1097/01.ju.0000101047.64379.d4
M3 - Article
C2 - 14767340
AN - SCOPUS:12144288255
SN - 0022-5347
VL - 171
SP - 1314
EP - 1318
JO - Investigative Urology
JF - Investigative Urology
IS - 3
ER -
