Identifying the Molecular Mechanism of Tumor Suppression by Maspin in Breast Cancer
Annual rept. 15 Apr 2003-14 Apr 2004
BAYLOR COLL OF MEDICINE HOUSTON TX
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Maspin is a unique member of the serpin family that shares extensive homology with monocyte-neutrophil elastase inhibitor, PAI-2 and other serpins. Initially identified as a class II tumor suppressor gene, maspin has been shown to inhibit invasion and motility of mammary tumors. When maspin gene was introduced into breast tumor cells, it was demonstrated that tumor transfectants expressing maspin exhibited significant decrease in breast tumor growth and metastasis in nude mice. Maspin gene expression is not detected in most breast tumors and loss of its expression is correlated with tumor invasiveness. Maspin is also found to be a potent angiogenesis inhibitor. Based on the previous work by my laboratory and other colleagues, I hypothesize that maspin possesses multiple functionality that requires its interaction with multiple target proteins. Maspin could act intracellularly or be secreted to act in a paracrine fashion on adjacent cells. I propose to isolate maspin targets by combined genetic and biochemical approaches. Once the target is identified, deletion and mutagenesis studies will be carried out to identify the functional domain of maspin that is responsible for such protein-protein interaction. Finally, such interaction will be verified in mammalian cells.
- Anatomy and Physiology
- Medicine and Medical Research