Identifying the Molecular Mechanism of Tumor Suppression by Maspin in Breast Cancer

Abstract

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 target(s) 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.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2003
Accession Number
ADA420082

Entities

People

  • Ming Zhang

Organizations

  • Baylor College of Medicine

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Fungi
  • Gene Expression
  • Inhibitors
  • Mammary Glands
  • Materials
  • Medical Personnel
  • Multiple Targets
  • Neoplasms
  • Protein-Protein Interactions
  • Proteins
  • Targets

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology