Update on exploring the tumors of multiple endocrine neoplasia type 1 in mouse models for basic and preclinical studies

• Published in: International journal of endocrine oncology Vol. 4; no. 3; pp. 113 - 116
• Main Author: Agarwal, Sunita K
• Format: Journal Article
• Language: English
• Published: London Future Medicine Ltd 01.08.2017
• Subjects: endocrine tumor; Endocrinology; epigenetic; Epigenetics; Genes; MEN1; menin; Mutation; Neuroendocrine tumors; Pancreas; PanNET; PNET; Rodents; tissue-specific; Tumorigenesis
• ISSN: 2045-0869; 2045-0877
• DOI: 10.2217/ije-2017-0013

Compound-mutant mice with germline homozygous deletion of the gene that encodes for the apoptosis repressor with CARD (ARC; Nol3-/- ) and Men1 deletion in the whole pancreas (Men1f/f ; Pdx1-Cre) did not alter PNET (insulinoma) burden (9). [...]ARC upregulation may not be a critical second hit in insulinoma formation. Compound-mutant mice with germline homozygous deletion of the gene that encodes for a TGF-β-related ligand ActivinB (InhβB-/- ) and β-cell-specific deletion of Men1 (Men1f/f ; Rip-Cre) did not affect insulinoma tumor growth but increased the survival of this mouse model by blocking the dedifferentiation of β-cells in the tumors (10). [...]ChIP-seq analysis of Men1 KO islets with anti-H3K4me3 or anti-H3K27me3, and gene expression analysis identified a number of menin-dependent target genes that showed loss of H3K4me3 and gain of H3K27me3 (16). Exploring this dynamic epigenetic regulation of gene expression during the development of Men1 KO tumors can help to study the molecular underpinnings of tumor progression that may help to identify therapeutic targets that are induced by menin loss.