RRC ID |
1461
|
著者 |
Furuta J, Kaneda A, Umebayashi Y, Otsuka F, Sugimura T, Ushijima T.
|
タイトル |
Silencing of the thrombomodulin gene in human malignant melanoma.
|
ジャーナル |
Melanoma Res
|
Abstract |
The loss of thrombomodulin (TM) expression is associated with tumour growth, infiltration and lymph node metastasis in human tumours. In melanoma cell lines, TM is reported to mediate cell adhesion, and its introduction into TM-negative melanoma cell lines suppresses their growth. In this study, we analysed TM expression in surgical melanoma specimens and the role of its promoter methylation in the loss of its expression. In 15 (75%) of the 20 specimens (five from a primary site and 15 from metastatic sites), melanoma cells lacked TM immunoreactivity. Methylation of the TM promoter region was detected in 10 (67%) of the 15 TM-negative specimens by methylation-specific polymerase chain reaction, whereas methylation was detected in two (40%) of the five TM-positive specimens. In cell lines, complete methylation of the TM promoter CpG island was detected in six (46%) of 13 melanoma cell lines, whereas no methylation was detected in two cultured normal melanocytes. There was a good correlation between the methylated status of the CpG island and the loss of TM messenger RNA (mRNA) expression. Treatment of melanoma cell lines with a demethylating agent, 5-aza-2'-deoxycytidine, induced demethylation of the promoter CpG island and the restoration of mRNA and protein expression. These findings suggest that most human melanomas lack TM expression, and that methylation of the promoter CpG island is one of the mechanisms responsible.
|
巻・号 |
15(1)
|
ページ |
15-20
|
公開日 |
2005-2-1
|
DOI |
10.1097/00008390-200502000-00004
|
PII |
00008390-200502000-00004
|
PMID |
15714116
|
MeSH |
Antimetabolites, Antineoplastic / pharmacology
Azacitidine / analogs & derivatives*
Azacitidine / pharmacology
Cells, Cultured
CpG Islands / genetics
DNA Methylation*
Decitabine
Gene Expression Regulation, Neoplastic*
Gene Silencing*
Humans
Melanocytes / metabolism
Melanoma / genetics*
Melanoma / surgery
Polymerase Chain Reaction
Promoter Regions, Genetic / genetics*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Skin Neoplasms / genetics
Skin Neoplasms / surgery
Thrombomodulin / genetics*
|
IF |
2.75
|
引用数 |
17
|
WOS 分野
|
DERMATOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
COLO 679(RCB0989)
MMAc(RCB0808) |