Constitutional activation of IL-6-mediated JAK/STAT pathway through hypermethylation of SOCS-1 in human gastric cancer cell line
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摘要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'-azadeoxycytidine 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.
著者To KF, Chan MWY, Leung WK, Ng EKW, Yu J, Bai AHC, Lo AWI, Chu SH, Tong JHM, Lo KW, Sung JJY, Chan FKL
期刊名稱British Journal of Cancer
出版年份2004
月份10
日期4
卷號91
期次7
出版社NATURE PUBLISHING GROUP
頁次1335 - 1341
國際標準期刊號0007-0920
電子國際標準期刊號1532-1827
語言英式英語
關鍵詞gastric caner; IL-6; methylation; SOCS-1; STAT3
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-15-09 於 02:35