title: The Levels of H11/HspB8 DNA methylation in human melanoma tissues and xenografts are a critical molecular marker for 5-Aza-2'-deoxycytidine therapy.
abstract: 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 β-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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore, USA.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Smith
authors.forename: Baiquan
authors.initials: B
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Kie-Sok
authors.initials: KS
authors.lastname: Lee
authors.forename: Laure
authors.initials: L
authors.lastname: Aurelian
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000502:physiology; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine; D000077209:Decitabine; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C413214:HSPB8 protein, human