Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas

Koen M.A. Dreijerink, Radhika A. Varier, Rick van Nuland, Roel Broekhuizen, Gerlof D. Valk, Jacqueline E. van der Wal, Cornelis J.M. Lips, J. Alain Kummer, H. Th Marc Timmers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a heriditary syndrome characterised by the occurrence of parathyroid, gastroenteropancreatic and pituitary tumours. The MEN1 gene product, menin, co-activates gene transcription by recruiting histone methyltransferases for lysine 4 of histone H3 (H3K4). We investigated whether in MEN1 tumours global changes in H3K4 trimethylation (H3K4me3) occur or whether alterations in gene expression can be observed. By immunohistochemistry we found that global levels of H3K4me3 are not affected in MEN1-related parathyroid adenomas. Menin can interact directly with the vitamin D receptor (VDR) and enhance the transcriptional activity of VDR. Messenger RNA levels of VDR target genes CYP24 and KLK6 were significantly lower in MEN1 parathyroid adenomas compared to normal tissue. Thus, aberrant gene expression in MEN1 tumours is not caused by lower global H3K4me3, but rather by specific effects on genes that are regulated by menin-interacting proteins, such as VDR.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume313
Issue number1-2
DOIs
Publication statusPublished - 10 Dec 2009

Cite this

Dreijerink, K. M. A., Varier, R. A., van Nuland, R., Broekhuizen, R., Valk, G. D., van der Wal, J. E., ... Timmers, H. T. M. (2009). Regulation of vitamin D receptor function in MEN1-related parathyroid adenomas. Molecular and Cellular Endocrinology, 313(1-2), 1-8. https://doi.org/10.1016/j.mce.2009.08.020