Investigation of DLEC1 gene methylation pattern in the human colorectal cancer cell line HT29 engineered by E- cadherin stable down regulation

Methylation of high-density CpG regions known as CpG Islands (CGIs) has been widely described as a mechanism associated with gene expression regulation. Changes in promoter methylation are considered as a hallmark of some cancers or cancer stem cells. DLEC1 (Deleted in Lung and Esophageal Cancer 1) is a protein coding gene and acts as a tumor suppressor gene by inhibiting cell proliferation. DLEC1 mediates tumor-suppressive activities through NF-κB signaling. Down regulation of this gene has been observed in several human cancers. In our previous study, we derived a cancer stem cell like population from HT29 (human colorectal adenocarcinoma cell line) by lentivirus mediated down regulation of E-cadherin gene. It has been shown that dysregulation of E-cadherin promotes dysfunctions of some signaling pathways such as Wnt signaling, Rho GTPases, and NF-κB pathway and influences cell survival, invasion, and migration in carcinogenesis The aim of this study was to investigate the DLEC1 gene methylation pattern in HT29 cell line and its derived cancer stem cell like population by MSP (Methylated Specific PCR) method. Our results demonstrated that DLEC1 gene has a hyper methylated state in HT29 cell line engineered by E- cadherin stable down regulation in comparison with intact HT29 cell line. These findings may imply that how epigenetic deregulation of NF-κB pathway can contribute to form a cancer stem cell like phenotype.

کلیدواژه ها:

Methylation ، HT29 ، stem cell ، DLEC1 ، E-cadherin