Methylation of the E-cadherin gene promoter correlates with progression ofprostate cancer

Purpose: We studied the methylation status of E-cadherin gene promoter in p rostate cancer and its relationship with E-cadherin inactivation in prostat e cancer. Materials and Methods: Seven human prostate cell lines and 35 microdissecte d prostate cancer specimens were analyzed for E-cadherin promoter methylati on using the bisulfite genome sequencing technique. E-cadherin messenger (m )RNA expression and protein expression were also studied in prostate cell l ines by reverse transcriptase-polymerase chain reaction and in prostate can cer specimens by immunostaining, respectively. Results: The overall methylation of E-cadherin promoter was evident in 14 o f 20 grades III to V (70%) and in 5 of 15 grades I to II (33%) prostate can cer samples. It correlated with absent or reduced E-cadherin immunostaining . Methylation in low grade tumors was present mainly in the exon region, wh ereas in high grade tumors methylation was also present in the promoter reg ion. Methylation was noted in 2 of 6 prostate cancer cell lines (33%) and c orrelated well with decreased E-cadherin mRNA in these cell lines. Treatmen t with the demethylating agent 5-aza-2'-deoxycytidine restored E-cadherin m RNA levels in the E-cadherin negative prostate cancer cell lines TSUPr1 and DuPro. Conclusions: Methylation of the E-cadherin gene is common in prostate cance r and the severity of E-cadherin methylation correlates with tumor progress ion. This study implies that the invasion and metastasis suppressor functio n of E-cadherin may often be compromised in human prostate cancer by epigen etic rather than by mutational events.