Hypermethylation associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas.
We recently demonstrated inactivation in hepatocellular carcinomas (HCCs) of the gene encoding SOCS1/JAB1/SSI-1, a JAK-binding protein that regulates the JAK/STAT signal-transduction pathway. In a follow-up immunochemical investigation of expression of SOCS-1 in hepatoblastomas (HBLs), the protein was markedly reduced in half of the HBL tumors we examined. CpG-rich regions upstream of the SOCS-1 gene were hypermehylated in 7 of the 15 HBL cases. The results suggest that hypermethylation may play an important role in silencing the SOCS-1 gene, not only in adult HCCs, but also in liver tumors arising in childhood.
Nagai
Hisaki
H
Department of Molecular Biology and Pathology, Institute of Gerontology, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki 211-0063, Japan.
Naka
Tetsuji
T
Terada
Yoshie
Y
Komazaki
Toshiaki
T
Yabe
Aya
A
Jin
Enjing
E
Kawanami
Oichi
O
Kishimoto
Tadamitsu
T
Konishi
Noboru
N
Nakamura
Mitsutoshi
M
Kobayashi
Yasuhito
Y
Emi
Mitsuru
M
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002648:Child; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D018197:Hepatoblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; 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