| First Author | Wagh PK | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 6 | Pages | 2735-46 |
| PubMed ID | 22474186 | Mgi Jnum | J:186728 |
| Mgi Id | MGI:5432980 | Doi | 10.1210/en.2011-1543 |
| Citation | Wagh PK, et al. (2012) Conditional deletion of beta-catenin in mammary epithelial cells of Ron receptor, Mst1r, overexpressing mice alters mammary tumorigenesis. Endocrinology 153(6):2735-46 |
| abstractText | The Ron receptor tyrosine kinase (macrophage stimulating 1 receptor) is overexpressed in approximately 50% of human breast cancers. Transgenic mice overexpressing Ron in the mammary epithelium [mouse mammary tumor virus driven (MMTV)-Ron expressing mice] develop mammary tumors that exhibit up-regulation of beta-catenin and beta-catenin target genes. beta-Catenin has been shown to be a mediator of mammary tumorigenesis in various breast cancer models, including downstream of Ron. However, the in vivo impact of a conditional loss of beta-catenin downstream of Ron receptor overexpression on the onset, growth, turnover, and metastasis of mammary tumors has not been addressed. To determine the significance of beta-catenin in the context of Ron overexpression, we conditionally deleted beta-catenin in mammary epithelial cells of MMTV-Ron mice. Conditional deletion of beta-catenin in the mammary epithelium, through the use of whey acidic protein (WAP)-Cre transgenic mice, significantly delayed the onset of mammary hyperplastic nodules, the presence of palpable mammary tumors, and ultimately decreased liver metastasis. beta-Catenin loss in this model was also associated with decreased expression of cyclin D1. In total, these studies support an important role for beta-catenin downstream of Ron receptor signaling during the development of mammary tumorigenesis. |
