Purkinje cell protein 4 expression is associated with DNA methylation status in aldosterone-producing adenoma.

Related Articles

Purkinje cell protein 4 expression is associated with DNA methylation status in aldosterone-producing adenoma.

J Clin Endocrinol Metab. 2017 Dec 26;:

Authors: Kobuke K, Oki K, Gomez-Sanchez CE, Ohno H, Itcho K, Yoshii Y, Yoneda M, Hattori N

Abstract
CONTEXT: Aldosterone production is stimulated by activation of calcium signaling in aldosterone-producing adenoma (APA), and epigenetic factors such as DNA methylation may be associated with the expression of genes involved in aldosterone regulation.
OBJECTIVE: Our aim was to investigate the DNA methylation of genes related to calcium signaling cascades in APA, and the association of mutations in genes linked to APA with DNA methylation levels.
METHODS: Non-functioning adrenocortical adenoma (NF, n=12) and APA (n=35) samples were analyzed. The KCNJ5 T158A mutation was introduced into human adrenocortical cell lines (HAC15 cells) using lentiviral delivery. DNA methylation array analysis was conducted using adrenal tumor samples and HAC15 cells.
RESULTS: The Purkinje cell protein 4 (PCP4) gene was one of the most hypo-methylated in APA. DNA methylation levels in two sites of PCP4 showed a significant inverse correlation with the mRNA expression in adrenal tumors. Bioinformatics and multiple regression analysis revealed that CEBPA (CCAAT/enhancer binding protein alpha) may bind to the methylation site of PCP4 promoter. CEBPA bound to PCP4 hypo-methylated region by Chromatin immunoprecipitation assay. There was no significant difference of PCP4 methylation levels among APA genotypes. Moreover, KCNJ5 T158A did not influence PCP4 methylation levels in HAC15 cells.
CONCLUSIONS: We showed that the PCP4 promoter was one of the most hypo-methylated in APA, and PCP4 transcription may be associated with demethylation as well as CEBPA in APA. KCNJ5 mutations known to result in aldosterone overproduction were not related with PCP4 methylation in either clinical or in vitro studies.

PMID: 29294065 [PubMed - as supplied by publisher]

http://ift.tt/2AhJOR2