연사 : 허근 교수 (경북대)
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
연제 : Epigenetic changes of retrotransposons in human colorectal cancer metastasis
일시 : 2015년 5월 29일 (금) 오후 4시
장소 : 하나과학관 A동 101호
초청교수 : 지성욱 교수
Abstract
Global hypomethylation of cytosines within CpG dinucleotides is one of the distinguishing features of the neoplastic cells in human cancers. More specifically, hypomethylation of evolutionarily conserved repetitive elements (Alu and LINE-1) is associated with increased chromosomal instability in colorectal cancer (CRC). Recent data indicates that transcription start sites of certain proto-oncogenes are located within these repeat elements, and increased hypomethylation of these regions may induce the expression of illegitimate oncogenic transcripts. Primary CRCs demonstrate frequent global Alu and LINE-1 hypomethylation; however, it is unclear whether hypomethylation of these repeat sequences may be associated with a metastatic phenotype. This study was aimed to determine the role of increased hypomethylation of Alu and LINE-1 sequences in CRC metastasis development. We analyzed a panel of CRC cells with different metastatic potential, as well as tissues from CRC patients with matched primary colon cancer and corresponding liver metastasis tissues. Alu and LINE-1 methylation levels were determined by quantitative bisulfite pyrosequencing. Our results provide evidence that increased Alu and LINE-1 hypomethylation is a novel feature of liver metastasis from CRC. We speculate that hypomethylation of these repeat elements may inadvertently permit activation of previously silenced proto-oncogenes, which may facilitate a more aggressive malignant phenotype in these advanced stage cancers.