RRC ID |
41956
|
Author |
Guan X, Sagara J, Yokoyama T, Koganehira Y, Oguchi M, Saida T, Taniguchi S.
|
Title |
ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma.
|
Journal |
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.
|
Volume |
107(2)
|
Pages |
202-8
|
Published |
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
|
Times Cited |
74
|
WOS Category
|
ONCOLOGY
|
Resource |
Human and Animal Cells |
C32TG(RCB1929)
HMV-I(RCB0004)
HMV-II(RCB0777)
SK-MEL-28(RCB1930)
G-361(RCB0991) |