Epigenetic inactivation of SOCS-1 by CpG island hypermethylation in human gastric carcinoma.
Suppressor of cytokine signaling (SOCS)-1 inhibits signaling of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway by several cytokines and has tumor suppressor activity. Methylation of the SOCS-1 CpG island has been shown to inactivate the SOCS-1 gene in certain human cancers. In our study, we investigated methylation status of the SOCS-1 gene by methylation-specific PCR in 75 gastric carcinoma (GC) tissues, 25 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals. We also performed bisulfite sequencing of DNAs from 2 GC tissues. In addition, SOCS-1 mRNA levels were examined in 50 GCs by quantitative RT-PCR. Hypermethylation of the SOCS-1 gene was detected in 33 (44%) of 75 GC tissues and in 3 (12%) of 25 corresponding nonneoplastic mucosae; the incidence was significantly different (p = 0.004). None of the 10 normal gastric tissues from healthy individuals showed hypermethylation. Methylation of the SOCS-1 gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS-1 in GC tissues (p = 0.009, 0.034 and 0.002, respectively). Reduced expression of SOCS-1 in GC tissues was associated with lymph node metastasis and advanced tumor stage (p = 0.013 and 0.002, respectively). Our results suggest that transcriptional inactivation of the SOCS-1 gene by hypermethylation may be involved in development, progression and metastasis of GC.
Oshimo
Yasuhiro
Y
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Kuraoka
Kazuya
K
Nakayama
Hirofumi
H
Kitadai
Yasuhiko
Y
Yoshida
Kazuhiro
K
Chayama
Kazuaki
K
Yasui
Wataru
W
D002277:Carcinoma / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014158:Transcription, Genetic
D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins