PMID- 17455252
OWN - NLM
STAT- MEDLINE
DCOM- 20070912
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 121
IP  - 4
DP  - 2007 Aug 15
TI  - Global expression profiling of murine MEN1-associated tumors reveals a regulatory 
      role for menin in transcription, cell cycle and chromatin remodelling.
PG  - 776-83
AB  - 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.
FAU - Mould, Arne W
AU  - Mould AW
AD  - Division of Cancer Cell Biology, Queensland Institute of Medical Research, 
      Herston, QLD, Australia.
FAU - Duncan, Russell
AU  - Duncan R
FAU - Serewko-Auret, Magdalena
AU  - Serewko-Auret M
FAU - Loffler, Kelly A
AU  - Loffler KA
FAU - Biondi, Christine
AU  - Biondi C
FAU - Gartside, Michael
AU  - Gartside M
FAU - Kay, Graham F
AU  - Kay GF
FAU - Hayward, Nicholas K
AU  - Hayward NK
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Animals
MH  - *Cell Cycle
MH  - *Chromatin Assembly and Disassembly
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Biological
MH  - Neoplasms, Experimental/*genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pancreatic Neoplasms/genetics
MH  - Pituitary Neoplasms/genetics
MH  - Proto-Oncogene Proteins/*genetics/*physiology
MH  - Reproducibility of Results
MH  - *Transcription, Genetic
EDAT- 2007/04/25 09:00
MHDA- 2007/09/13 09:00
CRDT- 2007/04/25 09:00
PHST- 2007/04/25 09:00 [pubmed]
PHST- 2007/09/13 09:00 [medline]
PHST- 2007/04/25 09:00 [entrez]
AID - 10.1002/ijc.22734 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Aug 15;121(4):776-83. doi: 10.1002/ijc.22734.