Alteration of Cadherin 3 Expression and DNA Methylation in Association with Aggressive Renal Cell Carcinoma

被引:6
作者
Tabrizi, Pouriya Faraj [1 ]
Peters, Inga [2 ]
Schimansky, Inga [1 ]
Dubrowinskaja, Natalia [1 ]
Reese, Christel [1 ]
Tezval, Hossein [1 ]
Kuczyk, Markus Antonius [1 ]
Serth, Juergen [1 ]
机构
[1] Hannover Med Sch, Dept Urol & Urol Oncol, D-30625 Hannover, Germany
[2] Krankenhaus NW Frankfurt, Dept Urol, D-60488 Frankfurt, Germany
关键词
renal cell carcinoma; DNA methylation; cancer epigenetics; CDH3; expression; COMPREHENSIVE MOLECULAR CHARACTERIZATION; P-CADHERIN; FACTOR RECEPTOR; CANCER; TUMORS; GENE; IDENTIFICATION; METASTASIS; INDICATOR; BEHAVIOR;
D O I
10.3390/ijms242216476
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cadherins (calcium-dependent adhesion proteins) are important in cellular adhesion and may play a role in the development and progression of renal cell carcinoma (RCC). This study investigated changes in cadherin 3 (CDH3; P-cadherin) mRNA expression, DNA methylation, and protein expression in RCC and compared the results with the histopathological and clinical characteristics of patients. The possible contribution of CDH3 to tumor cell invasiveness was tested in a functional assay using siRNA-based suppression of CDH3 expression and subsequent real-time impedance analysis using a Matrigel invasion model. Our analyses revealed a tumor-specific loss of CDH3 mRNA expression, CDH3 DNA hypermethylation, and loss of distal tubular and collecting duct CDH3 protein expression in RCC. A relatively higher methylation level in tumors was associated with a loss of cell differentiation and higher clinical stage. siRNA-induced suppression of CDH3 expression modulated the invasion characteristics of tumor cells in the impedance-based real-time cellular analysis. Our results indicate that loss of CDH3 expression is common in RCC and may contribute to the pathogenesis of a subset of RCC. Further studies to reveal the mechanisms of loss of expression and its effects on the invasive behavior of renal tumor cells are required.
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页数:17
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