Menin and p53 have non-synergistic effects on tumorigenesis in mice

Loffler, Kelly A., Mould, Arne W., Waring, Paul M., Hayward, Nicholas K. and Kay, Graham F. (2012) Menin and p53 have non-synergistic effects on tumorigenesis in mice. BMC Cancer, 12 252.1-252.16. doi:10.1186/1471-2407-12-252

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Author Loffler, Kelly A.
Mould, Arne W.
Waring, Paul M.
Hayward, Nicholas K.
Kay, Graham F.
Title Menin and p53 have non-synergistic effects on tumorigenesis in mice
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2012-06
Sub-type Article (original research)
DOI 10.1186/1471-2407-12-252
Open Access Status DOI
Volume 12
Start page 252.1
End page 252.16
Total pages 16
Place of publication London, England, U.K.
Publisher BioMed Central
Collection year 2013
Language eng
Formatted abstract
While it is now more than a decade since the first description of the gene mutation underlying the tumour predisposition syndrome multiple endocrine neoplasia type 1 (MEN1), the mechanism by which its protein product menin acts to prevent development of tumours is still poorly understood.

We undertook a genetic experiment to assess whether menin synergises with p53. Mice carrying various combinations of Men1 and Trp53 mutations were generated then survival and pathology assessed.


While homozygous loss of Trp53 in mice resulted in early onset, aggressive tumours and profoundly reduced lifespan, heterozygous loss of either Trp53 or Men1 caused later onset disease, with a spectrum of tumours characteristic of each tumour suppressor gene. Loss of one copy of Men1 in animals also lacking both alleles of Trp53 did not exacerbate phenotype, based on survival, animal weight or sites of pathology, compared to Trp53 deletion alone. Dual heterozygous deletion of Men1 and Trp53 resulted in a small reduction in lifespan compared to the individual mutations, without new tumour sites. Median number of pathology observations per animal was increased in dual heterozygous animals compared with heterozygous loss of Trp53 alone.

Simultaneous heterozygous deletion of Men1 in animals with either heterozygous or homozygous deletion of Trp53 did not result in formation of tumours at any new sites, implying additive rather than synergistic effects of these pathways. Mice that were Men1+/- in addition to Trp53+/- had tumours in endocrine as well as other sites, implying that increase in total tumour burden, at sites typically associated with either Men1 or Trp53 loss, contributed to the slight decrease in survival in Men1+/-: Trp53+/- animals in comparison with their littermates.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Medicine Publications
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Created: Thu, 02 Aug 2012, 00:23:28 EST by Matthew Lamb on behalf of School of Medicine