Deletion or mutation of the MEN1 gene, which encodes the epigenetic regulator menin, specifically induces poorly differentiated neuroendocrine tumors; however, the biological and clinical importance of MEN1 in the nervous system remains poorly understood.
The concordance of menin staining between primary tumor and metastasis in most cases suggests that menin loss is an early event in PanNET tumorigenesis.
In recent years, preclinical studies have identified potential new therapeutic targets for treating MEN1-associated neuroendocrine tumours (including PNETs), and these include epigenetic modification, the β-catenin-wingless (WNT) pathway, Hedgehog signalling, somatostatin receptors and MEN1 gene replacement therapy.This Review discusses these advances.
Conversely, inhibition of MME in NET cells repressed proliferation and tumor growth in vivo Our findings reveal a previously unappreciated cross-talk between two crucial tumor suppressor genes thought to work by independent pathways, focusing on MME as a common target of menin/Daxx to treat NET.
Neuroendocrine tumors (NETs) of the pancreas (PNETs) and bronchus (BNETs), which may have 5-year survivals of <50% and as low as 5%, respectively, represent targets for such drugs, as >40% of PNETs and ~35% of BNETs have mutations of the multiple endocrine neoplasia type 1 (MEN1) gene, which encodes menin that modifies histones by interacting with histone methyltransferases.
Somatic mutations of three potential tumor-related genes (HRAS, PAK1 and MEN1) might contribute to the tumorigenesis of thymic neuroendocrine tumors with EAS.
Rats affected by the MENX (MEN1-like) syndrome share some features with MEN1 patients albeit they bear a germline mutation in <i>Cdkn1b</i> (p27) and not in <i>Men1</i> Both <i>Men1</i>-knockout mice and MENX rats have been exploited for therapy-response studies testing novel drugs for efficacy against neuroendocrine tumors (NETs) and have provided promising leads for novel therapies.
Menin, the product of the Men1 gene, which is frequently mutated in pancreatic neuroendocrine tumors, acts as a chromatin-remodeling factor to modulate the transcription of cell cycle regulators by interacting with histone modification factors.
Here we sought to investigate PGRN expression and regulation after exposure to hypoxia as well as its effects on pancreatic islet cells and neuroendocrine tumors (NETs) in MEN1(+/−) mice.
Insulinomas (pancreatic islet β cell tumors) are the most common type of functioning pancreatic neuroendocrine tumors that occur sporadically or as a part of the MEN1 syndrome that is caused by germ line mutations in MEN1.
The aim of this study was to characterize the molecular basis of a case of MEN1-like syndrome with a neuroendocrine tumor and persistent primary hyperparathyroidism (PHPT).
Altered MENIN expression is one of the few events that are clearly associated with foregut neuroendocrine tumours (NETs), classical oncogenes or tumour suppressors being not involved.
46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs).