RRC ID 59832
著者 Ichikawa T, Nakahata S, Fujii M, Iha H, Shimoda K, Morishita K.
タイトル The regulation of NDRG2 expression during ATLL development after HTLV-1 infection.
ジャーナル Biochim Biophys Acta Mol Basis Dis
Abstract N-myc downstream-regulated gene 2 (NDRG2) is a candidate tumor suppressor that is frequently downregulated in adult T-cell leukemia/lymphoma (ATLL) and functions to negatively regulate several cellular signaling pathways as PP2A recruiter. To clarify the molecular mechanisms of suppression of NDRG2 expression, we initially determined the expression pattern of NDRG2 in various types of T-cells and ATLL cells. NDRG2 expression was significantly upregulated in HTLV-1/Tax-immortalized T-cells, which was mediated by NF-κB activation through Tax expression. On the other hand, NDRG2 expression was suppressed in HTLV-1-infected cell lines and various types of ATLL cells, which was dependent on the DNA methylation of the NDRG2 promoter. We found that the expression of enhancer of zeste homolog 2 (EZH2), a member of the polycomb family, is increased in ATLL, and that EZH2 directly binds to the NDRG2 promoter and induces DNA methylation of the NDRG2 promoter. Since the expression of EZH2 were anti-parallelly regulated with the NDRG2 expression, EZH2 might be one of the most important regulators of the downregulation of NDRG2, contributing to enhanced activation of signaling pathways during ATLL development.
巻・号 1865(10)
ページ 2633-2646
公開日 2019-10-1
DOI 10.1016/j.bbadis.2019.07.001
PII S0925-4439(19)30224-8
PMID 31295529
MeSH Adult Cell Line, Tumor Cell Proliferation DNA Methylation Down-Regulation Enhancer of Zeste Homolog 2 Protein / metabolism Gene Expression Regulation, Neoplastic HTLV-I Infections / complications* Human T-lymphotropic virus 1 Humans Leukemia-Lymphoma, Adult T-Cell / genetics* Leukemia-Lymphoma, Adult T-Cell / metabolism* NF-kappa B / metabolism Signal Transduction T-Lymphocytes Tumor Suppressor Proteins / genetics* Tumor Suppressor Proteins / metabolism* Up-Regulation
IF 4.328
引用数 1
リソース情報
ヒト・動物細胞 293T(RCB2202)