This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Okochi, O. Articles by Nakao, A. Search for Related Content PubMed PubMed Citation Articles by Okochi, O. Articles by Nakao, A.

Methylation-Mediated Silencing of SOCS-1 Gene in Hepatocellular Carcinoma Derived from Cirrhosis

Second Department of Surgery, Nagoya University School of Medicine, Nagoya, Japan

Purpose: Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of Janus kinase and signal transducer and activation of transcription pathway. Recently, it was demonstrated that SOCS-1 gene was silenced frequently by methylation of CpG island in human hepatocellular carcinoma (HCC). We examined the methylation-mediated silencing of SOCS-1 in tumors of HCC patients.

Experimental Design: Fifty patients with HCC were investigated in this study. We examined the methylation status of the SOCS-1 promoter region by methylation-specific PCR and then confirmed the methylation-mediated silencing of SOCS-1 by Northern blot analysis. Furthermore, this methylation status was compared with clinicopathological findings.

Results: Aberrant methylation of the SOCS-1 gene was detected in 30 of 50 (60%) HCC specimens. No corresponding nontumorous liver tissues showed SOCS-1 methylation. Subsequent Northern analysis proved that methylation of the SOCS-1 promoter inactivated translation and diminished expression of SOCS-1 mRNA. We then analyzed the correlation between the clinicopathological data and SOCS-1 aberrant methylation and found that HCC derived from liver cirrhosis had a significant relationship with SOCS-1 methylation (P = 0.0207).

Conclusions: SOCS-1 may be a novel tumor suppressor, and its aberrant methylation may be a key event for HCC transformation of cirrhotic nodules.

This article has been cited by other articles:

				Y. Masuhiro, K. Kayama, A. Fukushima, K. Baba, M. Soutsu, Y. Kamiya, M. Gotoh, N. Yamaguchi, and S. Hanazawa SOCS-3 Inhibits E2F/DP-1 Transcriptional Activity and Cell Cycle Progression via Interaction with DP-1 J. Biol. Chem., November 14, 2008; 283(46): 31575 - 31583. [Abstract] [Full Text] [PDF]

				Y. Y. Sanders, A. Pardo, M. Selman, G. J. Nuovo, T. O. Tollefsbol, G. P. Siegal, and J. S. Hagood Thy-1 Promoter Hypermethylation: A Novel Epigenetic Pathogenic Mechanism in Pulmonary Fibrosis Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 610 - 618. [Abstract] [Full Text] [PDF]