Investigation of Alpha6 Integrins and Their Signaling Intermediates as Prognostic Markers for Breast Cancer
Abstract
Our goal was to evaluate the expression of alpha6beta4 integrin in breast carcinoma and to test whether increased alpha6beta4-mediated signaling correlates with poor prognosis in breast cancers that overexpress alpha6beta4. We found that the beta4 gene does not appear to be amplified in breast cancers that overexpress the alpha6beta4 integrin. We designed a probe for beta4 mRNA useful in evaluating alpha6beta4 expression in formalin-fixed, paraffin-embedded tissues, and showed that beta4 mRNA expression appears not to be a prognostic factor in node-negative invasive breast carcinoma. Adhesion-independent cross-linking of alpha6beta4 was found to be associated with phosphorylation of nonmusole myosin II heavy chain, which may affect actin-myosin filament organization. We showed by immunofluorescence microscopy that cell-surface alpha6beta4 clustering can be demonstrated following antibody- mediated cross-linking of the integrin not only in cell lines but also in fine-needle aspirates of breast carcinoma specimens. Although we could not demonstrate clinical significance in this study, further refinements are needed in the techniques to induce and detect integrin clustering in carcinoma specimens in order to determine whether detection of integrin clustering as a surrogate of integrin function will ultimately prove to be useful clinically.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425749
Entities
People
- Michael Z. Gilcrease
Organizations
- The University of Texas MD Anderson Cancer Center