中国肺癌杂志2016，Vol.19Issue(9)：565-570,6.DOI:10.3779/j.issn.1009-3419.2016.09.01
H2228细胞和EML4-ALK阳性肺癌组织中SOCS3基因启动子区甲基化状态的研究
Methylation Status of theSOCS3 Gene Promoter in H2228 Cells and EML4-ALK-positive Lung Cancer Tissues
摘要
Abstract
Background and objective TheEML4-ALK fusion gene is a newly discovered driver gene of non-small cell lung cancer and exhibits special clinical and pathological features. hTe JAK-STAT signaling pathway, an important downstream signaling pathway of EML4-ALK, is aberrantly sustained and activated in EML4-ALK-positive lung cancer cells fusion gene, but the underlying reason remains unknown. hTe suppressor of cytokine signaling (SOCS) is a negative regula-tory factor that mainly inhibits the proliferation, differentiation, and induction of apoptotic cells by inhibiting the JAK-STAT signaling pathway. hTe aberrant methylation of theSOCS gene leads to inactivation of tumors and abnormal activation of the JAK2-STAT signaling pathway. hTe aim of this study is to investigate the methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 cells and lung cancer tissues.Methods hTe methylation status of the SOCS3 promoter in EML4-ALK-positive H2228 lung cancer cells and lung cancer tissues was detected by methylation-speciifc PCR (MSP) analysis and veri-ifed by DNA sequencing. hTe expression levels of SOCS3 in H2228 cells were detected by Western blot and Real-time PCR analyses atfer treatment with the DNA methyltransferase inhibitor 5'-Aza-dC.Results MSP and DNA sequencing assay results indicated the presence of SOCS3 promoter methylation in H2228 cells as well as in three cases of seven EML4-ALK-positive lung cancer tissues. hTe expression level of SOCS3 signiifcantly increased in H2228 cells atfer 5′-Aza-dC treatment.Conclu-sion hTe aerrant methylation of the SOCS3 promoter region in EML4-ALK (+) H2228 cells and lung cancer tissues may be signiifcantly involved in the pathogenesis of EML4-ALK-positive lung cancer.关键词
肺肿瘤/EML4/ALK/SOCS3/DNA甲基化Key words
Lung neoplasms/Echinoderm microtubule-associated-protein-like 4 (EML4)/Anaplastic lymphoma kinase (ALK)/Suppressor of cytokine signaling 3 (SOCS3)/DNA methylation引用本文复制引用
刘春来,李永文,董云龙,张洪兵,李颖,刘红雨,陈军..H2228细胞和EML4-ALK阳性肺癌组织中SOCS3基因启动子区甲基化状态的研究[J].中国肺癌杂志,2016,19(9):565-570,6.基金项目
本研究受国家自然科学基金项目（No.81172233和No.81372306）、天津自然科学基金重点项目（No.12JCZDJC24400和No.16JCZDJC34200）、天津自然科学基金项目（No.13JCYBJC22600）、天津市科委抗癌重大专项攻关计划（No.12ZCDZSY16100）、教育部博士点基金（No.20131202110004）资助This study was supported by grants from the National Natural Science Foundation of China (to Jun CHEN)(No.81172233)(to Hongyu LIU)(No.81372306), the Tianjin key project of Natural Science Foundation (to Jun CHEN)(No.12JCZDJC24400 and No.16JCZDJC34200), Tianjin Natural Science Foundation (to Hongyu LIU)(No.13JCYBJC22600), Tianjin Science and Technology Support Program(to Jun CHEN)(No.12ZCDZSY16100) and the Ph.D. Programs Foundation from Ministry of Education of China (to Jun CHEN)(No.20131202110004) （to Jun CHEN）
