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.
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 humanhepatocellular carcinoma (HCC). We examined the methylation-mediated silencing of SOCS-1 in tumors of HCCpatients. 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.
Authors: R C Sobti; Neha Singh; Showket Hussain; Vanita Suri; Raje Nijhawan; A C Bharti; Mausumi Bharadwaj; B C Das Journal: Cell Oncol (Dordr) Date: 2011-09-21 Impact factor: 6.730
Authors: Yan Y Sanders; Annie Pardo; Moisés Selman; Gerard J Nuovo; Trygve O Tollefsbol; Gene P Siegal; James S Hagood Journal: Am J Respir Cell Mol Biol Date: 2008-06-12 Impact factor: 6.914