title: Conditional deletion of β-catenin in mammary epithelial cells of Ron receptor, Mst1r, overexpressing mice alters mammary tumorigenesis.
abstract: 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 β-catenin and β-catenin target genes. β-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 β-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 β-catenin in the context of Ron overexpression, we conditionally deleted β-catenin in mammary epithelial cells of MMTV-Ron mice. Conditional deletion of β-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. β-Catenin loss in this model was also associated with decreased expression of cyclin D1. In total, these studies support an important role for β-catenin downstream of Ron receptor signaling during the development of mammary tumorigenesis.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.
authors.forename: Purnima K
authors.initials: PK
authors.lastname: Wagh
authors.forename: Glendon M
authors.initials: GM
authors.lastname: Zinser
authors.forename: Jerilyn K
authors.initials: JK
authors.lastname: Gray
authors.forename: Archana
authors.initials: A
authors.lastname: Shrestha
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waltz
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006965:Hyperplasia; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics*
chemical_list: D051176:beta Catenin; D019938:Cyclin D1; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases