You have accessJournal of UrologyBladder Cancer: Basic Research III1 Apr 20121069 ABERRATION OF A CELL ADHESION MOLECULE, CADM1, AND ITS PATHOLOGICAL OR BIOLOGICAL SIGNIFICANCE IN URINARY BLADDER CANCER Taketo Kawai, Akiteru Goto, Masayoshi Nagata, Miwako Iwai, Teppei Morikawa, Shigeki Morita, Haruki Kume, Masashi Fukayama, Yukio Homma, and Yoshinori Murakami Taketo KawaiTaketo Kawai Tokyo, Japan More articles by this author , Akiteru GotoAkiteru Goto Akita, Japan More articles by this author , Masayoshi NagataMasayoshi Nagata Tokyo, Japan More articles by this author , Miwako IwaiMiwako Iwai Tokyo, Japan More articles by this author , Teppei MorikawaTeppei Morikawa Tokyo, Japan More articles by this author , Shigeki MoritaShigeki Morita Tokyo, Japan More articles by this author , Haruki KumeHaruki Kume Tokyo, Japan More articles by this author , Masashi FukayamaMasashi Fukayama Tokyo, Japan More articles by this author , Yukio HommaYukio Homma Tokyo, Japan More articles by this author , and Yoshinori MurakamiYoshinori Murakami Tokyo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1175AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Tumor suppressor CADM1 (cell adhesion molecule 1) belongs to the immunoglobulin-superfamily cell adhesion molecules (IgCAMs) and participates in cell-cell adhesion activity in various epithelia, including those of urinary bladder. On the other hand, CADM1 is frequently inactivated in a variety of human cancers chiefly by gene promoter methylation, especially in their advanced stages. In this study, we investigated possible involvement of CADM1 in bladder cancer. METHODS CADM1 expression in 11 human bladder cancer cell lines was examined by RT-PCR analysis and western blotting analysis. The methylation status of the CADM1 gene promoter in bladder cancer cell lines was examined by pyrosequencing analysis. CADM1 expression in 147 human primary bladder cancers was examined by immunohistochemical analysis. Cadm1-deficient mice as well as the wild-type C57BL/6 mice were administrated 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), an established bladder carcinogen for mice, in the drinking water for 20 weeks. Any human examination was conducted according to the protocol approved by the research ethics committee of Graduated School of Medicine, The University of Tokyo. RESULTS CADM1 expression was absent or greatly reduced in 6 of 11 human bladder cancer cell lines. The promoter methylation of the CADM1 gene was observed in 4 of those 6 cell lines. CADM1 was expressed along the cell membrane in normal urothelium of human bladder. On the other hand, membranous expression was lost or altered in 92 (63%) of 147 primary bladder cancers. Loss or aberrant expression of CADM1 was significantly correlated with higher pT stages (pTa < pT1 < pT2-4), higher nuclear grade (G1-2 < G3). Moreover, loss or aberrant expression was closely correlated with poor prognosis (P < 0.001) and was an independent prognostic factor in multivariate analysis (P = 0.021) in 112 patients treated with radical cystectomy. Administration of BBN developed invasive bladder cancers (pT2-4) at significantly higher incidence in Cadm1-deficient mice than in the wild-type mice (P = 0.025). CONCLUSIONS The disruption of CADM1 would be involved in the progression of bladder cancers, especially in the invasion and metastasis, and could provide a prognostic marker in invasive bladder cancer. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e434 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taketo Kawai Tokyo, Japan More articles by this author Akiteru Goto Akita, Japan More articles by this author Masayoshi Nagata Tokyo, Japan More articles by this author Miwako Iwai Tokyo, Japan More articles by this author Teppei Morikawa Tokyo, Japan More articles by this author Shigeki Morita Tokyo, Japan More articles by this author Haruki Kume Tokyo, Japan More articles by this author Masashi Fukayama Tokyo, Japan More articles by this author Yukio Homma Tokyo, Japan More articles by this author Yoshinori Murakami Tokyo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...