A molecular signature of cell invasion in breast ca

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DESCRIPTION (provided by applicant): The long-term objective of this research project is to unveil the molecular signature of tumor cell invasion. Tumor invasion and metastasis are complex processes involving extracellular matrix (ECM) degrading proteinase activity and cell migration through the ECMs. Since mounting evidence suggests that ras expression serves as a marker for tumor aggressiveness of breast cancer, we have investigated ras-mediated signaling pathways critical for human breast epithelial cell invasion. Our study showed that H-ras, but not N-ras, induces migrative and invasive phenotypes involving matrix metalloproteinase (MMP)-2 upregulation, while both Hand N-ras induce cell proliferation and transformation. Since ras is among the most frequently activated signaling molecules in human cancer, we hypothesize that the mRNA expression pattern differentially regulated by H-ras and N-ras reflects a signature representing invasive and migrative capability of cancer cells. To test our hypothesis, during the Phase I study we propose (Aim 1) to further investigate the molecular pathways for the ras-mediated cell migration and invasion; (Aim 2 and 3) to identify mRNA marker candidates of H-ras-mediated breast epithelial cell migration/invasion by microarrays; (Aim 4) to verify clinical relevance of differential mRNA expression profile associated with cell migration and invasion; and (Aim 5) to test feasibility of identifying phosphorylated and/or secreted protein marker candidates. The accomplishment of these aims will help us design diagnostic tools to predict primary tumors with metastatic potential.