Global expression profiling of murine MEN1-associated tumors reveals a regulatory role for menin in transcription, cell cycle and chromatin remodelling

Mould, Arne W., Duncan, Russell, Serewko-Auret, Magdalena, Loffler, Kelly A., Biondi, Christine, Gartside, Michael, Kay, Graham F. and Hayward, Nicholas K. (2007) Global expression profiling of murine MEN1-associated tumors reveals a regulatory role for menin in transcription, cell cycle and chromatin remodelling. International Journal of Cancer, 121 4: 776-783. doi:10.1002/ijc.22734


Author Mould, Arne W.
Duncan, Russell
Serewko-Auret, Magdalena
Loffler, Kelly A.
Biondi, Christine
Gartside, Michael
Kay, Graham F.
Hayward, Nicholas K.
Title Global expression profiling of murine MEN1-associated tumors reveals a regulatory role for menin in transcription, cell cycle and chromatin remodelling
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2007
Sub-type Article (original research)
DOI 10.1002/ijc.22734
Volume 121
Issue 4
Start page 776
End page 783
Total pages 8
Editor H. zur Hausen
Place of publication Hoboken, U.S.A.
Publisher John Wiley & Sons
Collection year 2008
Language eng
Subject C1
1117 Public Health and Health Services
1112 Oncology and Carcinogenesis
Abstract 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. © 2007 Wiley-Liss, Inc.
Keyword knockout mice
microarray
multiple endocrine neoplasia type 1
p18
p16
chromatin modification
regulation of transcription
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 02 May 2008, 14:05:36 EST by Brenda Mason on behalf of Medicine - Royal Brisbane and Women's Hospital