The Levels of H11/HspB8 DNA Methylation in Human Melanoma Tissues and Xenografts Are a Critical Molecular Marker for 5-Aza-2′-Deoxycytidine Therapy

被引：23

作者：

Smith, Cynthia C. ^{[1
]}

Li, Baiquan ^{[1
]}

Liu, Juan ^{[1
]}

Lee, Kie-Sok ^{[1
]}

Aurelian, Laure ^{[1
]}

机构：

[1] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA

来源：

CANCER INVESTIGATION | 2011年 / 29卷 / 06期

基金：

美国国家卫生研究院;

关键词：

Gene expression; Molecular biology; Cutaneous melanoma; Therapy; Prognosis and response predictions; HEAT-SHOCK-PROTEIN; MALIGNANT-MELANOMA; BETA-CATENIN; H11; KINASE; CYCLIN-E; METHYLTRANSFERASE PROMOTER; TUMOR-SUPPRESSOR; TP53; MUTATIONS; CELL-GROWTH; APOPTOSIS;

D O I：

10.3109/07357907.2011.584588

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

H11/HspB8 is a functionally distinct small heat shock protein. It causes growth arrest in melanocytes, associated with the inhibition of Cyclin E/Cdk2 and beta-catenin phosphorylation at the transcriptional activity site Ser(552) and is silenced through DNA methylation in 27/35 (77%) melanoma tissues/early cultures. 5-Aza-2 '-deoxycytidine (Aza-C) induces melanoma cell death correlated with the levels of H11/HspB8 DNA methylation (p < .001). In line with low/moderate H11/HspB8 methylation, PI3-K inhibition increases Aza-C-induced cell death. Aza-C inhibits the growth of melanoma xenografts related to the levels of H11/HspB8 methylation, and a nonmethylated/non-TAK1 binding H11/HspB8 mutant confers Aza-C resistance. H11/HspB8 is a potential molecular marker for demethylation therapies.

引用

页码：383 / 395

页数：13

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