Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice
| Autor: | Margaret Coster, Guadalupe Polanco-Echeverry, Ian Tomlinson, Jacqueline Haines, Thomas Guenther, Peter Rogers, Jun Wang, Amy McCart, Andrew Latchford, Oliver M. Sieber, Nirosha Suraweera, Andrew Silver |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Genetic Markers
medicine.medical_specialty Genes APC Adenoma Adenomatous polyposis coli Familial adenomatous polyposis Mice Gene Frequency Inbred strain Pregnancy Internal medicine Genetics medicine Animals Humans Genetic Predisposition to Disease Allele Receptor Molecular Biology Allele frequency Genetics (clinical) biology Chromosome Mapping General Medicine medicine.disease Mice Mutant Strains Disease Models Animal Endocrinology Adenomatous Polyposis Coli Receptors Estrogen Genetic marker biology.protein Female Pregnancy Complications Neoplastic |
| Zdroj: | Human molecular genetics. 15(23) |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | 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 5 0.015). Our results provide the first experimental evidence for genetic determinants controlling pregnancy-associated tumourigenesis; analogous genetic factors may exist in humans. |
| Databáze: | OpenAIRE |
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