Adhesion-Linked Protein Tyrosine Phosphatases, Morphogenesis and Breast Cancer Progression
Abstract
Stromal-epithelial interactions regulate mammary epithelial cell (MEC) fate via integrin-growth factor receptor (GFR) interactions. Integrin-GFR crosstalk influences MEC behavior through activation of tyrosine kinase signaling that is tempered by protein tyrosine phosphatase (PTP) activity of which we know little about. Using a degenerate RT-PCR to amplify PTPs expressed in differentiated versus non-differentiated MECs, we identified the Band 4.1 PTPs MEG1 and Dl as two candidate PTP metastasis suppressors. Our studies show that during MEC differentiation PTP MEGl and Dl expression rise dramatically, coincident with assembly of E-cadherin/Beta-catenin adherens junction formation. However, both mRNA and protein expression of MEGl and Dl become repressed following MEC tissue differentiation. Because we could not establish any correlation between MEC growth, or tissue polarization, this suggests that MEG1 and Dl expression may be functionally linked to adherens junction assembly. Consistently, malignant MECs that fail to assemble adherens junctions do not modulate MEGl or Dl expression. Moreover, MEGl expression is not induced in phenotypically reverting tumors, or down regulated in dormant structures. This suggests that these Band 4.1 PTPs may be functionally-linked to molecules mediating adherens junction formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA435265
Entities
People
- Valerie M Weaver
Organizations
- University of Pennsylvania