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

12 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

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