Research Abstracts Online
January 2010 - March 2011
University of Minnesota Twin Cities
of Laboratory Medicine and Pathology
PI: Kathryn Schwertfeger
FGFR1 and IL-1B Cooperate to Promote Mammary Tumorigenesis
Inflammation within the tumor microenvironment is a risk factor for tumor development and is often associated with poor prognosis in cancer. Previous results from an in vivo mouse model of mammary tumorigenesis demonstrated that inflammatory cytokines such as Interleukin-1 beta (IL-1beta) promote oncogene-induced epithelial proliferation induced by fibroblast growth factor receptor 1 (FGFR1) in the mammary epithelium. FGFR1, a growth factor receptor that promotes transformation of breast cancer cells, is amplified in a significant percentage of breast cancers and recent studies have linked FGFR1 expression to poor response to breast cancer therapy. Additionally, many studies have found that inappropriate expression of IL-1beta in breast cancer patients is associated with poor clinical prognosis. A major focus of this research focuses on identifying the roles of inflammatory cytokines and other inflammatory molecules in mediating the initiation and promotion of breast cancer.
Using mouse epithelial cell lines that express an inducible form of FGFR1 (iFGFR1), these researchers have investigated the roles of FGFR1 and IL-1beta in epithelial proliferation and migration. These systems have been used to study downstream signaling pathways of FGFR1 and IL-1beta both in vivo and in vitro. Notably, they have observed a synergy of action between the iFGFR1 and IL-1beta pathways that cooperate to induce downstream gene targets that neither pathway induces on its own. They used a microarray analysis to identify potential gene targets of these cooperating pathways. Access to the Genespring program and Integrated Pathways Analysis has been and will continue to be necessary to analyze the results.
Johanna Ecklund Reed, Graduate Student