Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas

被引:52
作者
Knobbe, CB
Reifenberger, J
Blaschke, B
Reifenberger, G
机构
[1] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany
[2] Univ Dusseldorf, Dept Dermatol, D-40225 Dusseldorf, Germany
关键词
D O I
10.1093/jnci/djh064
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The carboxyl-terminal modulator protein (CTMP) has been identified as a negative regulator of protein kinase B/Akt. Aberrant Akt signaling is frequently observed in glioblastomas, the most common and most malignant glial brain tumors. Because loss of CTMP function and/or expression may remove the inhibitory effects on Akt and promote tumorigenesis, we studied 93 primary glioblastomas and nine glioblastoma cell lines for CTMP deletion, mutation, promoter hypermethylation, and mRNA expression. None of the tumors or cell lines had CTMP-homozygous deletions or coding sequence mutations. However, CTMP mRNA expression was lower by at least 50% relative to nonneoplastic brain tissue in 37 (40%) glioblastomas and six (67%) glioma cell lines. Reduced CTMP mRNA levels were closely associated with hypermethylation of the CTMP promoter. Furthermore, treatment of CTMP-hypermethylated A172 glioma cells with the demethylating agent 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A resulted in partial demethylation of the CTMP promoter and increased CTMP mRNA expression. Thus, epigenetic downregulation of CTMP transcription is a common aberration in glioblastomas.
引用
收藏
页码:483 / 486
页数:4
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