Correlation between T-cadherin gene expression and aberrant methylation of T-cadherin promoter in human colon carcinoma cells.

Previous researches showed T-cadherin (CDH13) expression was downregulated in colon cancer tissues and was associated with increase of invasive and metastatic potential. This research was to observe the mechanisms responsible for inactivation of T-cadherin gene in colon carcinoma; we investigated the methylation status around the 5' promoter region of T-cadherin gene of Hct116 colon cancer cell line by methylation-specific polymerase chain reaction (MSP), also detected the expression change of T-cadherin mRNA and protein in Hct116 cell line after 5-Aza-CdR treatment by reverse transcriptase polymerase chain reaction and Western blotting, and compared the T-cadherin methylation status with T-cadherin mRNA and protein expression. We found that hypermethylation of T-cadherin was involved in Hct116 cell line, while T-cadherin mRNA and protein expression was almost lost or downregulated in Hct116 cell line. Therefore, methylation of the T-cadherin promoter region was correlated with the loss or downregulation of T-cadherin mRNA and protein expression in Hct116 colon cancer cell line. Treatment of T-cadherin-negative carcinoma cells with the demethylating agent, 5-aza-2'-deoxycytidine, induced re-expression of this gene. Our findings demonstrate that 5' CpG island methylation is common in colon carcinoma and may play an important role in the inaction of T-cadherin. Our results also suggest that demethylation of the T-cadherin gene may be a potential therapeutic strategy for colon carcinoma.