SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation

Abstract Members of the suppressor of cytokine-induced signaling (SOCS) family are negative regulators of cytokine signaling pathways. By mRNA differential display, we showed that SOCS6 was frequently down-regulated in gastric cancer (GC). Our data showed that allelic loss and promoter hypermethylat...

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Bibliographic Details
Published in:Cancer letters 2010-02, Vol.288 (1), p.75-85
Main Authors: Lai, Rai-Hua, Hsiao, Ya-Wen, Wang, Mei-Jung, Lin, Huan-Yu, Wu, Chew-Wun, Chi, Chin-Wen, Li, Anna Fen-Yau, Jou, Yuh-Shan, Chen, Jeou-Yuan
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Aged
Apoptosis
Cell growth
Cell Line, Tumor
Cell Proliferation
Cytokines
Deoxyribonucleic acid
DNA
DNA Methylation
Down-Regulation
Female
Females
Gastric cancer
Gene Expression Regulation, Neoplastic
Genes
Growth suppression
Hematology, Oncology and Palliative Medicine
Humans
Kinases
Loss of Heterozygosity
Male
Membrane Potential, Mitochondrial
Middle Aged
Mortality
Promoter hypermethylation
Promoter Regions, Genetic
Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Signal transduction
SOCS6
Stomach Neoplasms - genetics
Stomach Neoplasms - metabolism
Stomach Neoplasms - pathology
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - metabolism
Time Factors
Transfection
Tumor Stem Cell Assay
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Summary:Abstract Members of the suppressor of cytokine-induced signaling (SOCS) family are negative regulators of cytokine signaling pathways. By mRNA differential display, we showed that SOCS6 was frequently down-regulated in gastric cancer (GC). Our data showed that allelic loss and promoter hypermethylation may account for the major mechanisms leading to SOCS6 inactivation. Ectopic expression of SOCS6 suppressed cell growth and colony formation, in part through eliciting intrinsic apoptotic pathway, accompanied with decreased mitochondrial membrane potential. Taken together, this study provides molecular and functional data supporting the importance of loss-of-function of SOCS6 as a frequent event in gastric tumorigenesis.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.06.025