Differential expression of the tumor suppressor A-kinase anchor protein 12 in human diffuse and pilocytic astrocytomas is regulated by promoter methylation

Benjamin Goeppert, Christopher R. Schmidt, Lea Geiselhart, Céline Dutruel, David Capper, Marcus Renner, Monika Nadja Vogel, Cornelia Zachskorn, Jenny Zinke, Benito Campos, Peter Schmezer, Odilia Popanda, Wolfgang Wick, Michael Weller, Richard Meyermann, Jens Schittenhelm, Patrick Nikolaus Harter, Perikles Simon, Wilko Weichert, Peter SchirmacherChristoph Plass, Michel Mittelbronn*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

The scaffold protein A-kinase anchor protein 12 (AKAP12) exerts tumor suppressor activity and is downregulated in several tumor entities. We characterized AKAP12 expression and regulation in astrocytomas, including pilocytic and diffusely infiltrating astrocytomas. We examined 194 human gliomas and 23 normal brain white matter samples by immunohistochemistry or immunoblotting for AKAP12 expression. We further performed quantitative methylation analysis of the AKAP12 promoter by MassARRAY® of normal brain, World Health Organization (WHO) grade I to IV astrocytomas, and glioma cell lines. Our results show that AKAP12 is expressed in a perivascular distribution in normal CNS, strongly upregulated in tumor cells in pilocytic astrocytomas, and weakly expressed in diffuse astrocytomas of WHO grade II to IV. Methylation analyses revealed specific hypermethylation of AKAP12α promoter in WHO grade II to IV astrocytomas. Restoration experiments using 5-aza-2′- deoxycytidine in primary glioblastoma cells decreased AKAP12α promoter methylation and markedly increased AKAP12α mRNA levels. In summary, we demonstrate that AKAP12 is differentially expressed in human astrocytomas showing high expression in pilocytic but low expression in diffuse astrocytomas of all WHO-grades. Our results further indicate that epigenetic mechanisms are involved in silencing AKAP12 in diffuse astrocytomas; however, a tumor suppressive role of AKAP12 in distinct astrocytoma subtypes remains to be determined.

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number10
DOIs
Publication statusPublished - Oct 2013
Externally publishedYes

Keywords

  • AKAP12
  • Astrocytoma
  • Gravin
  • Promoter methylation
  • SSeCKS

Fingerprint

Dive into the research topics of 'Differential expression of the tumor suppressor A-kinase anchor protein 12 in human diffuse and pilocytic astrocytomas is regulated by promoter methylation'. Together they form a unique fingerprint.

Cite this