Adhesion-Linked Protein Tyrosine Phosphatases, Morphogenesis and Breast Cancer Progression
Abstract
Stromal-epithelial interactions regulate breast cell fate via integrin-growth factor receptor interactions that activate tyrosine kinases that are tempered by protein tyrosine phosphatases (PTPP). Through various screening approaches we identified and profiled PTP expression in normal, malignantly transformed and phenotypically-reverted breast tissue and identified the Band 4.1 PTPs MEG1 and D1 as candidate PTP metastasis suppressor genes. We demonstrated that MEG1 and D1 expression rise dramatically early during mammary morphogenesis in response to cues from a compliant laminin-rich basement membrane that inhibit focal adhesion maturation and promote adherens junction assembly. The expression of PTP MEG1 and D1 is thereafter rapidly down regulated coincident with polarity and growth arrest. We also found that MEG1 and D1 levels are altered in tumors and that a stiffer tumor-associated stroma disrupts tissue organization and MEG and D1 expression and promotes malignant behavior of MECs. Because inhibiting mechanical force could restore tissue organization and normalize MEG and D1 expression, we are currently exploring the possibility that a reactive stiffer ECM stroma might drive malignant transformation of the breast by altering PTP function to disrupt tissue organization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA465847
Entities
People
- Valerie M Weaver
Organizations
- University of Pennsylvania