Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice

N. Suraweera, Jacqueline Haines, A. McCart, P. Rogers, A. Latchford, M. Coster, G. Polanco-Echeverry, T. Guenther, J. Wang, O. Sieber, I. Tomlinson, A. R. Silver

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Min mice provide a good model of human familial adenomatous polyposis. Recently, we have reported on two recombinant inbred lines (I and V) and the location of a modifier (Mom3) close to Apc, which altered polyp numbers in our mice possibly by modifying the frequency of wild-type (WT) allele loss at Apc; mice with severe disease (line V) showed elevated rates of loss. We now show that in line I only, a single pregnancy caused a significant increase in adenoma multiplicity compared with virgin controls (P < 0.001) and that an additional pregnancy conferred a similar risk. Pregnancy was linked to both adenoma initiation and enhanced tumour growth in line I mice, and interline crosses indicated that susceptibility to pregnancy-associated adenomas was under genetic control. We found no evidence for the involvement of oestrodial metabolizing genes or the oestrogen receptors (Esr1 and 2) in tumour multiplicity. Importantly, a significantly elevated frequency of WT allele loss at Apc was observed in adenomas from parous mice (line and backcrossed) carrying the line I Min allele relative to equivalent virgin controls (P = 0.015). Our results provide the first experimental evidence for genetic determinants controlling pregnancy-associated tumourigenesis; analogous genetic factors may exist in humans.

Original languageEnglish
Pages (from-to)3429-3435
Number of pages7
JournalHuman Molecular Genetics
Volume15
Issue number23
DOIs
Publication statusPublished - 1 Dec 2006

Bibliographical note

Funding Information:
Kevin Whitehill, Rachael Bartram and Pat Hillier (all of Health Protection Agency and staff of the Cancer Research Clare Hall laboratories) for technical assistance. This work was supported in part by Commission of European Communities Contract Grant FI4P-CT95-0008 and Cancer Research UK.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

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