Genetic Dissection of the Role of Heparan Sulfate in Mammary Tumor Progression
Annual rept. 1 Jun 2007-31 May 2008
BURNHAM INST LA JOLLA CA
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Heparan sulfate HS binds growth factors, protein-degrading enzymes, and other bioactive proteins, and to regulate their activities. Many of these proteins have strong implications in human breast cancer. There is also evidence that cellular HS production itself exerts strong influences on tumorigenesis, exemplified by the fact that mutations of Ext1, the gene encoding an HS synthesizing enzyme, cause multiple bone tumors. Furthermore, the level of HS degrading activity correlates with the aggressiveness of the tumor. Despite these long-standing observations, much less is known about the mechanisms by which HS influences the malignant behavior of tumors in vivo. Also important is the fact that HS is produced not only by tumor cells themselves but also by stromal cells that constitute the tumor microenvironment. This project will conduct cohort study using genetic mouse models to address these key questions. The first year of this project was dedicated mainly to establish, expand, and intercross mouse models for generating experimental cohorts. We have also characterized the gene recombination pattern induced by the FSP1-Cre transgenic mouse, which will be used to manipulate the expression of HS in tumor stromal cells.
- Medicine and Medical Research