title: The Ron receptor tyrosine kinase is not required for adenoma formation in Apc(Min/+) mice.
abstract: The Ron receptor tyrosine kinase is overexpressed in approximately half of all human colon cancers. Increased Ron expression positively correlates with tumor progression, and reduction of Ron levels in human colon adenocarcinoma cells reverses their tumorigenic properties. Nearly all colon tumors demonstrate loss of the adenomatous polyposis coli (APC) tumor suppressor, an early initiating event, subsequently leading to beta-catenin stabilization. To understand the role of Ron in early stage intestinal tumorigenesis, we generated Apc-mutant (Apc(Min/+)) mice with and without Ron signaling. Interestingly, we report here that significantly more Apc(Min/+) Ron-deficient mice developed higher tumor burden than Apc(Min/+) mice with wild-type Ron. Even though baseline levels of intestinal crypt proliferation were increased in the Apc(Min/+) Ron-deficient mice, loss of Ron did not influence tumor size or histological appearance of the Apc(Min/+) adenomas, nor was beta-catenin localization changed compared to Apc(Min/+) mice with Ron. Together, these data suggest that Ron may be important in normal intestinal tissue homeostasis, but that the expression of this receptor is not required for the formation and growth of adenomas in Apc(Min/+) mice.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Meyer
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waltz
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Goss
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D017931:DNA Primers; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases