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Schwertfeger_K

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
Medical School
Department of Laboratory Medicine and Pathlogy

PI: Kathryn Schwertfeger

Inflammation Cooperates With Growth Factor Signaling Pathways 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-1b) promote oncogene-induced epithelial proliferation. The oncogene fibroblast growth factor receptor 1 (FGFR1) is a growth factor receptor that promotes transformation of breast cancer cells. It 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-1b 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-1b in epithelial proliferation and migration. These systems have been used to study downstream signaling pathways of FGFR1 and IL-1b both in vivo and vitro. Notably, they have observed a synergy of action between the iFGFR1 and IL-1b 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 has been necessary to analyze the results and further studies using the Integrated Pathways Analysis are being performed to better understand the functions of the regulated genes in breast cancer.

Group Members

Majken Hall, Research Associate
Ronald Leon, Research Associate
Johanna Reed, Adjunct Faculty Collaborator