Association of altered promoter methylation with expression level of the plakoglobin gene in both the ARO thyroid cancer cell line and cancer tissues

Plakoglobin (PKG) is a protein linking Cadherin adhesion receptors to the actin cytoskeleton and its overexpression has been known to suppress cell proliferation and tumorigenesis in thyroid cancer. We investigated the effect of 5-Aza-2′-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor, on the methylation status of the promoter and the expression of the plakoglobin gene in a thyroid carcinoma cell line (ARO) and cancer tissues. In cultures of the ARO cell incubated without the compound, five of the 15 CpG sites in the promoter spanning - 225 and - 54 were methylated at a % methylation range of 42 - 12.5. When the cells were treated with 5-Aza-CdR, all the methylated CpG sites were induced to be demethylated except one. In addition, a new methylation at one CpG site arose at level of 12.0%. The expression level of PKG decreased approximately 10-fold for the 5-Aza-CdR-treated cells compared to untreated cells. The alternation of promoter methylation and expression of PKG was also observed in the thyroid cancer tissues. These findings may possibly indicate that the specific methylation status at the plakoglobin promoter induces changes of the expression level of the gene in the thyroid cancer.