| First Author | Suraweera N | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 23 | Pages | 3429-35 |
| PubMed ID | 17062636 | Mgi Jnum | J:117129 |
| Mgi Id | MGI:3695647 | Doi | 10.1093/hmg/ddl419 |
| Citation | Suraweera N, et al. (2006) Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice. Hum Mol Genet 15(23):3429-35 |
| abstractText | 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. |
