RRC ID 68749
著者 Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Yamanaka R, Tanaka Y, Nukiwa T, Marquez VE, Ishikawa Y, Ichinose M, Aburatani H.
タイトル PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer.
ジャーナル Sci Rep
Abstract Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. Expression array analysis of 23 SCLC cases and 42 normal tissues revealed that EZH2 and other PRC2 members were highly expressed in SCLC. ChIP-seq for H3K27me3 suggested that genes with H3K27me3(+) in SCLC were extended not only to PRC2-target genes in ES cells but also to other target genes such as cellular adhesion-related genes. These H3K27me3(+) genes in SCLC were repressed significantly, and introduction of the most repressed gene JUB into SCLC cell line lead to growth inhibition. Shorter overall survival of clinical SCLC cases correlated to repression of JUB alone, or a set of four genes including H3K27me3(+) genes. Treatment with EZH2 inhibitors, DZNep and GSK126, resulted in growth repression of SCLC cell lines. High PRC2 expression was suggested to contribute to gene repression in SCLC, and may play a role in genesis of SCLC.
巻・号 3
ページ 1911
公開日 2013-1-1
DOI 10.1038/srep01911
PII srep01911
PMID 23714854
PMC PMC3665955
MeSH Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism Blotting, Western Case-Control Studies Cell Proliferation Chromatin Immunoprecipitation Enhancer of Zeste Homolog 2 Protein Fluorescent Antibody Technique Gene Expression Profiling Histones / metabolism Humans Indoles / pharmacology Jumonji Domain-Containing Histone Demethylases LIM Domain Proteins / genetics LIM Domain Proteins / metabolism* Lung / metabolism* Lung Neoplasms / genetics Lung Neoplasms / metabolism Lung Neoplasms / mortality* Oligonucleotide Array Sequence Analysis Polycomb Repressive Complex 2 / antagonists & inhibitors Polycomb Repressive Complex 2 / genetics Polycomb Repressive Complex 2 / metabolism* Prognosis Pyridones / pharmacology RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Small Cell Lung Carcinoma / genetics Small Cell Lung Carcinoma / metabolism Small Cell Lung Carcinoma / mortality* Survival Rate Tumor Cells, Cultured
IF 3.998
リソース情報
ヒト・動物細胞 Lu-130(RCB0465)