RRC ID 41956
著者 Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T, Taniguchi S.
タイトル ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma.
ジャーナル Int J Cancer
Abstract ASC/TMS1 is an adaptor protein activating caspase-1 that stimulates processing of proIL-1beta and proIL-18. ASC was reported to be aberrantly methylated and silenced in human breast cancers. In our present study, ASC expression was examined in 12 melanoma cell lines by Western blot analysis and in 18 benign melanocytic nevi and 32 melanoma tissues by immunohistochemical staining. ASC expression was absent or reduced in 7 of 12 (58.3%) cell lines and in 20 of 32 (62.5%) melanoma tissues, whereas all 18 benign melanocytic nevi showed intensive ASC expression. To investigate whether ASC silencing in melanoma is involved in aberrant methylation, methylation specific PCR was carried out. Five of ten (50%) melanoma tissues exhibited methylation in CpG island of ASC companied with reduced ASC expression. Six of twelve (50%) melanoma cell lines showed aberrant methylation in the ASC gene, and 4 of the 6 (66.7%) methylation positive cell lines exhibited reduced ASC expression. We characterized methylation patterns in melanoma cell lines by using bisulfite genomic sequencing, and found that the degree of aberrant methylation correlated with the level of reductive ASC expression. Treatment with demethylating agent 5-aza-2'-deoxycytidine resulted in both demethylation of the ASC gene and the upregulation of ASC expression in the methylation positive melanoma cell lines. Our study shows that ASC is downregulated in melanoma, and that its suppression is partially mediated by aberrant methylation.
巻・号 107(2)
ページ 202-8
公開日 2003-11-1
DOI 10.1002/ijc.11376
PMID 12949795
MeSH Apoptosis Azacitidine / pharmacology Blotting, Western CARD Signaling Adaptor Proteins Caspase 1 / metabolism* CpG Islands Cytoskeletal Proteins DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors DNA (Cytosine-5-)-Methyltransferases / genetics DNA (Cytosine-5-)-Methyltransferases / metabolism DNA Methylation* DNA Primers / chemistry DNA, Neoplasm / genetics Down-Regulation Enzyme Activation Gene Expression Regulation, Neoplastic Gene Silencing Humans Melanoma / genetics* Melanoma / metabolism Melanoma / pathology Nevus, Pigmented / genetics* Nevus, Pigmented / metabolism Nevus, Pigmented / pathology Polymerase Chain Reaction Proteins / genetics Proteins / metabolism* Skin Neoplasms / genetics* Skin Neoplasms / metabolism Skin Neoplasms / pathology Sulfites / metabolism Tumor Cells, Cultured
IF 5.145
引用数 74
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 C32TG(RCB1929) HMV-I(RCB0004) HMV-II(RCB0777) SK-MEL-28(RCB1930) G-361(RCB0991)