期刊
HUMAN PATHOLOGY
卷 43, 期 8, 页码 1300-1307出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2011.10.010
关键词
Epigenomics; Epithelial-mesenchymal transition (EMT); Histone demethylase; Lysine methylation; Sarcoma epigenetics; Sarcoma genomics; Sarcoma therapy
类别
资金
- Austrian National Bank [13349]
- EuroBonet Project [018814]
- IVO Foundation
Lysine-specific demethylase 1 (GeneID 23028), a flavin-dependent monoamine oxidoreductase and a histone demethylase, serves as an epigenetic coregulator of transcription. Lysine-specific demethylase 1 is up-regulated in neuroblastoma and in bladder, breast, colorectal, gastric, lung; and neuroendocrine cancers, and its overexpression drives the cell cycle of otherwise nontransformed human cells, suggesting oncogenic properties. Lysine-specific demethylase 1 was recently reported to be also overexpressed in several different mesenchymal tumors. We investigated lysine-specific demethylase 1 expression in over 500 sarcomas by gene expression profiling and tissue microarray-coupled immunohistochemical analyses and confirmed lysine-specific demethylase 1 overexpression in rhabdomyosarcoma and synovial sarcoma. We also show for the first time that lysine-specific demethylase 1 is also overexpressed in chondrosarcoma, Ewing's sarcoma, and osteosarcoma wherein it localizes in cell nuclei. We further show that a US Food and Drug Administration-approved drug that inhibits lysine-specific demethylase 1 also inhibits chondrosarcoma, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma cell growth in vitro. These data suggest that lysine-specific demethylase 1 plays a role in sarcoma pathology and that lysine-specific demethylase 1 inhibition strategies might represent a novel means to inhibiting growth of lysine-specific demethylase 1-overexpressing sarcomas. (C) 2012 Elsevier Inc. All rights reserved.
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