Although the identification of menin-interacting partners and other evidence 
support a role for menin, the multiple endocrine neoplasia type 1 gene (MEN1) 
product, in regulating gene expression, little is known about the cellular 
pathways dysregulated by menin loss during tumorigenesis. The mouse models of 
MEN1 accurately mimic the human syndrome and provide an opportunity to assess 
the transcriptional effects of Men1 deletion in different endocrine tumor types 
to identify common pathway aberrations underlying tumorigenesis in MEN1-affected 
tissues. We compared the global gene expression profiles of pituitary adenomas 
and pancreatic islet tumors with control tissues from wild-type littermates. 
Amongst the 551 differentially expressed genes was significant 
over-representation of genes associated with chromatin remodelling, 
transcription and cell cycling, including some genes known to encode 
menin-binding partners, e.g., Rhox5 and Mll1. Consistent with increased 
cell-cycle transition from G1 to S phase was an elevation of Cdc7 expression in 
the tumors, which was confirmed by qRT-PCR using independent samples. In support 
of previous findings in islet tumors, we found down-regulation of the cell-cycle 
regulator, p18, in both the pancreatic islet and pituitary adenomas, suggesting 
that reduced p18 levels may be important for Men1-related tumorigenesis in 
multiple tissues. Surprisingly, we identified increased p16 transcript in 
pancreatic islet and pituitary tumors. This was accompanied by increased 
cytoplasmic localization p16 protein in tumor cells. The specific genes and 
general pathways we have found to be commonly dysregulated in MEN1 tumors, 
provide a platform for determining their roles in endocrine tumorigenesis.