RRC ID 39949
Author Nakayama S, Sasaki A, Mese H, Alcalde RE, Tsuji T, Matsumura T.
Title The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas.
Journal Int. J. Cancer
Abstract Reduction of E-cadherin strongly relates to invasiveness and metastasis in vitro. To clarify CpG methylation around the promoter region of the E-cadherin gene in oral squamous cell carcinoma (SCC), we examined the DNA samples of various human SCC cell lines and primary oral SCC tissues by methylation-specific polymerase chain reaction (MSP). CpG methylation of the E-cadherin gene markedly correlated to the reduction of E-cadherin expression in human oral SCC cell lines. In primary oral SCC tissues, only 1 of 5 preserved E-cadherin-expressing tissues was methylated, whereas methylation was found in 17 (94.4%) of 18 E-cadherin-reduced tissues. Our results suggest that reduction of E-cadherin expression is associated with CpG methylation of the E-cadherin gene promoter. We recently established two cell lines with high and low metastatic potential, UM1 and UM2, from SCC primary tongue tissue of a patient. E-cadherin expression of high-metastatic UM1 was clearly lower than that of low-metastatic UM2, and MSP results showed CpG methylation in the UM1 but not the UM2 cell line. To investigate whether demethylation of CpG methylation of the E-cadherin gene could restore expression and function of E-cadherin, we treated UM1 with the demethylating agent 5-azacytidine (5-aza) and found that E-cadherin expression was indeed restored by demethylation. Moreover, in the demethylated UM1, invasion of the collagen gel was clearly suppressed compared with the untreated UM1. These results suggested that inactivation of E-cadherin expression resulted from CpG methylation of the gene promoter; a correlation between CpG methylation of the E-cadherin gene promoter and invasive potential was also suggested.
Volume 93(5)
Pages 667-73
Published 2001-9-1
DOI 10.1002/ijc.1386
PII 10.1002/ijc.1386
PMID 11477576
MeSH Antimetabolites, Antineoplastic / pharmacology Azacitidine / pharmacology Cadherins / biosynthesis Cadherins / drug effects Cadherins / genetics* Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism CpG Islands / genetics* DNA Methylation Gene Expression Regulation, Neoplastic* / drug effects Gene Silencing Humans Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Promoter Regions, Genetic / drug effects Promoter Regions, Genetic / genetics Tumor Cells, Cultured / drug effects
IF 4.982
Times Cited 57
Human and Animal Cells