Open AccessDeficiency of the Erc / mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice
Author(s) -
Zhang Danqing,
Kobayashi Toshiyuki,
Kojima Tetsuo,
Kanenishi Kenji,
Hagiwara Yoshiaki,
Abe Masaaki,
Okura Hidehiro,
Hamano Yoshitomo,
Sun Guodong,
Maeda Masahiro,
Jishage Kouichi,
Noda Tetsuo,
Hino Okio
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01846.x
Subject(s) - carcinogenesis , tsc2 , cancer research , mesothelin , protein kinase b , cell growth , cell adhesion , knockout mouse , biology , focal adhesion , pi3k/akt/mtor pathway , microbiology and biotechnology , chemistry , phosphorylation , cell , signal transduction , cancer , immunology , receptor , antigen , genetics , biochemistry
Genetic crossing experiments were performed between tuberous sclerosis‐2 ( Tsc2 ) KO and expressed in renal carcinoma ( Erc ) KO mice to analyze the function of the Erc / mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2 +/−; Erc −/− mice than in Tsc2 +/−; Erc +/+ and Tsc2 +/−; Erc +/− mice. Tumors from Tsc2 +/−; Erc −/− mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen‐coated plates in vitro was enhanced in Erc ‐restored cells and decreased in Erc ‐suppressed cells with siRNA. Tumor formation by Tsc2 ‐deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc ‐deficient/suppressed cells compared with Erc ‐expressed cells. These results indicate that deficiency of the Erc / mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell‐substrate adhesion via the integrin‐related signal pathway. ( Cancer Sci 2011; 102: 720–727)