論文 - 詳細
| RRC ID | 42223 |
|---|---|
| 著者 | To KF, Chan MW, Leung WK, Ng EK, Yu J, Bai AH, Lo AW, Chu SH, Tong JH, Lo KW, Sung JJ, Chan FK. |
| タイトル | Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line. |
| ジャーナル | Br J Cancer |
| Abstract |
The interleukin-mediated Janus kinase (JAK)/STAT pathway plays a crucial role in carcinogenesis. Recently, increased STAT3 activity was found in hepatocellular carcinoma and multiple myeloma in which there was silencing of SOCS-1 (suppressor of cytokine signalling-1) by gene promoter hypermethylation. We investigated the expression level of interleukin-6 (IL-6) and SOCS-1 in gastric cancer cell lines. Expression of SOCS-1 correlated with IL-6 level in most of the cell lines, except for AGS cells in which SOCS-1 was absent despite a high level of IL-6 production. Methylation analysis by methylation-specific polymerase chain reaction and bisulphite sequencing revealed that CpG island of SOCS-1 was densely methylated in AGS cells. Demethylation treatment by 5'aza-deoxycytidine restored SOCS-1 expression and also suppressed constitutive STAT3 phosphorylation in AGS cells. Moreover, methylation of SOCS-1 was detected in 27.5% (11 of 40) of primary gastric tumours samples, 10% (one of 10) of adjacent noncancer tissues but not in any (zero of nine) normal gastric mucosa. Methylation of SOCS-1 also correlated with the loss of mRNA expression in some primary gastric cancers. In conclusion, this is the first report to demonstrate that hypermethylation of SOCS-1 led to gene silencing in gastric cancer cell line and primary tumour samples. Downregulation of SOCS-1 cooperates with IL-6 in the activation of JAK/STAT pathway in gastric cancer. |
| 巻・号 | 91(7) |
| ページ | 1335-41 |
| 公開日 | 2004-10-4 |
| DOI | 10.1038/sj.bjc.6602133 |
| PII | 6602133 |
| PMID | 15354212 |
| PMC | PMC2409891 |
| MeSH | Carrier Proteins / biosynthesis Carrier Proteins / metabolism* Cell Transformation, Neoplastic DNA Methylation DNA-Binding Proteins / pharmacology* Down-Regulation Humans Interleukin-6 / pharmacology* Intracellular Signaling Peptides and Proteins* Janus Kinase 1 Protein-Tyrosine Kinases / pharmacology* RNA, Messenger / analysis RNA, Messenger / biosynthesis Repressor Proteins / biosynthesis Repressor Proteins / metabolism* Reverse Transcriptase Polymerase Chain Reaction STAT3 Transcription Factor Stomach Neoplasms / pathology* Suppressor of Cytokine Signaling 1 Protein Suppressor of Cytokine Signaling Proteins Trans-Activators / pharmacology* Tumor Cells, Cultured |
| IF | 5.791 |
| 引用数 | 72 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN28(RCB1000) MKN45(RCB1001) |