Research Abstracts Online
2008 - March 2009
University of Minnesota Twin Cities
Department of Laboratory Medicine and Pathology
PI: Kathryn Schwertfeger
Identification of Novel Transcriptional Targets in Mammary Epithelial Cells With Activated iFGFR1 and IL1-Beta Treatment
Increased invasiveness and poor prognosis in breast cancer is often associated with inflammation within the tumor microenvironment. Inflammation is a well-known risk factor for tumor development and is often associated with poor prognosis in cancer. A major focus in this lab is on the role of inflammation in promoting the initiating stages of breast cancer. Previous results from an in vivo mouse model of preneoplastic breast cancer formation demonstrated that inflammatory cytokines such as Interleukin-1 beta (IL1-beta) are involved in mediating epithelial proliferation induced by Fibroblast Growth Factor Receptor-1 (FGFR1) activation in the mammary epithelium. The current focus of the lab is to identify the potential roles of cytokines and other inflammatory molecules in mediating the various aspects of breast cancer initiation and promotion, including epithelial proliferation, angiogenesis, and host responses, using mouse models of mammary tumorigenesis as well as mammary epithelial cell lines.
Using a mouse mammary epithelial cell line, the researchers activated iFGFR1 and added exogenous IL1-beta. They then performed a microarray analysis to identify potential targets of these pathways. The use of GeneSpring Software has helped identify Hyaluronan Synthase 2 (HAS2) as a transcriptional target of both iFGFR activation and IL1β treatment. Interestingly, the receptor for HA, CD44, was also significantly up-regulated in the array results. These results indicate that the convergence of the FGFR1 pathway and IL1-beta induce the transcription and activation of the HAS2/HA/CD44 pathway. HA is a polysaccharide that plays a major role in the extracellular matrix, and provides an amenable microenvironment for proliferation and cell migration and may play an important role in breast cancer.
The researchers are currently validating the transcriptional targets identified by microarrays and GeneSpring software. They will be using GeneSpring to make further identifications of transcriptional targets in our system, as well as further defining the role of HAS2 in the iFGFR1 and IL1-beta pathway.
Ronald Leon, Research Associate