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CpG methylation of promoter region inactivates E‐cadherin gene in renal cell carcinoma
Author(s) -
Nojima Dana,
Nakajima Koichi,
Li LongCheng,
Franks Joseph,
RibeiroFilho Leopoldo,
Ishii Nobuhisa,
Dahiya Rajvir
Publication year - 2001
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.1060
Subject(s) - biology , dna methylation , demethylating agent , methylation , cpg site , microbiology and biotechnology , cancer research , promoter , gene , bisulfite sequencing , gene expression , genetics
Abstract CpG methylation in the promoter region has been shown to be important in the regulation of genes implicated in malignant transformation. The present study was designed to test the hypothesis that CpG methylation of the promoter region of the E‐cadherin gene may inactivate its expression in renal cell carcinoma. To test this hypothesis, five kidney cancer cell lines and 34 microdissected renal cell carcinoma samples were analyzed for gene and protein expression by reverse transcription–polymerase chain reaction and immunohistochemistry, respectively. CpG methylation in the promoter regions of the E‐cadherin gene was analyzed by the sodium bisulfite genome sequencing technique. Our results show that all normal renal tissue expressed the E‐cadherin gene and protein. Of the renal cancer tissues analyzed, 67% (23 of 34) lacked E‐cadherin expression, with an associated increase in methylation, compared with normal tissue. E‐cadherin gene promoter was methylated in all renal cancer cell lines and was accompanied by a loss of E‐cadherin gene and protein expression. The treatment of renal cancer cell lines with the demethylating agent 5‐aza‐2′‐deoxycytidine restored E‐cadherin mRNA expression in all renal cancer cell lines. This is the first report that shows inactivation of the E‐cadherin gene and protein in renal cell carcinoma through CpG hypermethylation in the promoter region of this gene. The results of these experiments may contribute to an understanding of the role of E‐cadherin inactivation in renal cell carcinoma. © 2001 Wiley‐Liss, Inc.