Prostaglandin E₂ Receptor Subtype 2 (EP₂) Null Mice are Protected Against Murine Lung Tumorigenesis

Abstract

Background: Manipulating prostaglandin (PG) production modulates tumor development. Elevated PGI₂ production prevents murine lung cancer, while decreasing PGE₂ content protects against colon cancer. PGE₂ receptor subtype 2 (EP₂)-deficient mice were hypothesized to be resistant to lung tumorigenesis. Materials and Methods: EP₂ null BALB/c mice and their wild-type littermates were exposed to an initiation-promotion carcinogenesis protocol and lung tumorigenesis was examined. Chronic lung inflammation was induced to determine whether EP₂ ablation influenced inflammatory cell infiltration. Results: Tumor multiplicity in EP₂ null mice was 34% lower than in their wild-type littermates (21.9±3.0 vs. 14.5±2.9 tumors/mouse, p<0.001). The lung tumor burden, an indicator of growth rate, also declined (57%, p<0.05). All the mice exhibited similar inflammatory cell infiltration. Conclusion: PGE₂, acting through EP₂, enhanced lung tumorigenesis through a mechanism that may be distinct from its pro-inflammatory activity. Thus, EP₂ is a potential target for novel chemoprevention strategies.