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Role of PTEN in the Tumor Microenvironment

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Annual rept. 15 May 2007-14 May 2008

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Recent scientific advances have revealed that a malignant tumor can be viewed as an organ consisting of different types of interacting cells. Different tumor cell types play different roles in the growth and development of the tumor and thus in the end, all cells within the tumor may help pave the way for further tumor growth in a patient with cancer. Current work in the field indicates that fibroblasts surrounding breast cancers are particularly important for cancer progression, but no one knows why. Our experimental approach to this problem is a direct one we target the mutation of genes in stromal fibroblasts surrounding the tumor in order to learn whether these genes are important for cancer progression. Using this approach we have shown that the Pten gene in fibroblasts is a major gene involved in suppressing epithelial breast cancers. In order to understand how Pten works in fibroblasts we will measure the immediate and long-term consequences of Pten mutation on the biology of all the cells surrounding the tumor, including the tumor cells themselves, as well as the matrix that holds these cells together. Because the entire system is so complex, we plan to study how the Pten gene behaves as a tumor suppressor by developing extremely detailed three-dimensional images of tumors where each image is annotated with detailed cancer related molecular information. This will allow us to use bioinformatics computer assisted methods to understand the molecular basis for how fibroblasts promote breast cancer. This information will lead to the design of novel therapeutic strategies that target fibroblasts and that could be used in combination with current therapies that target epithelial cells, to stop tumor growth and prevent reoccurrence or metastasis.

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  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

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