| First Author | Kovtun IV | Year | 2011 |
| Journal | Carcinogenesis | Volume | 32 |
| Issue | 7 | Pages | 1085-92 |
| PubMed ID | 21551128 | Mgi Jnum | J:173626 |
| Mgi Id | MGI:5049814 | Doi | 10.1093/carcin/bgr080 |
| Citation | Kovtun IV, et al. (2011) Increased incidence of endometrioid tumors caused by aberrations in E-cadherin promoter of mismatch repair-deficient mice. Carcinogenesis 32(7):1085-92 |
| abstractText | Loss of E-cadherin expression is a critical step in the development and progression of gynecological tumors. Study of the precise role of E-cadherin has been hampered by the lack of satisfactory mouse model for E-cadherin deficiency. Likewise, DNA mismatch repair (MMR) is implicated in gynecological tumorigenesis, but knockout of MMR in mice predominantly causes hematologic neoplasms. Here, we show that combined disruption of E-cadherin and DNA MMR pathways increases incidence of endometrioid tumors in mice. Twenty percent of mice knockout for Msh2 enzyme and hemizygous for E-cadherin [Msh2(-/-)/Cdh1(+/-)] developed endometrioid-like tumors in the ovary, uterus and genital area. Characteristic of these tumors was a complete loss of E-cadherin expression. Sequence analysis of E-cadherin promoter region demonstrated that the loss of E-cadherin expression is caused by inactivating mutations, implying that E-cadherin is a mutational target in Msh2-deficient mice. In addition, Msh2(-/-)/Cdh1(+/-) mice showed a reduction in overall survival as compared with their Msh2(-/-) counterparts due to the development of more aggressive lymphomas, suggesting a specific role of E-cadherin in lymphomagenesis. In conclusion, Msh2(-/-)/Cdh1(+/-) mice provide a good model of gynecological tumorigenesis and may be useful for testing molecular target-specific therapies. |
