METHYLATION OF THE E-CADHERIN GENE PROMOTER CORRELATES WITH PROGRESSION OF PROSTATE CANCER

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Abstract
We studied the methylation status of E-cadherin gene promoter in prostate cancer and its relationship with E-cadherin inactivation in prostate cancer. Seven human prostate cell lines and 35 microdissected prostate cancer specimens were analyzed for E-cadherin promoter methylation using the bisulfite genome sequencing technique. E-cadherin messenger (m)RNA expression and protein expression were also studied in prostate cell lines by reverse transcriptase-polymerase chain reaction and in prostate cancer specimens by immunostaining, respectively. The overall methylation of E-cadherin promoter was evident in 14 of 20 grades III to V (70%) and in 5 of 15 grades I to II (33%) prostate cancer samples. It correlated with absent or reduced E-cadherin immunostaining. Methylation in low grade tumors was present mainly in the exon region, whereas in high grade tumors methylation was also present in the promoter region. Methylation was noted in 2 of 6 prostate cancer cell lines (33%) and correlated well with decreased E-cadherin mRNA in these cell lines. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored E-cadherin mRNA levels in the E-cadherin negative prostate cancer cell lines TSUPr1 and DuPro. Methylation of the E-cadherin gene is common in prostate cancer and the severity of E-cadherin methylation correlates with tumor progression. This study implies that the invasion and metastasis suppressor function of E-cadherin may often be compromised in human prostate cancer by epigenetic rather than by mutational events.