The Roles of FGF-2, TGF Beta and TGF Beta Receptor 2 in Breast Cancer Dormancy
Abstract
We determined the expression of FGF-2 during steps of mammary ductal dedifferentiation as preliminary investigations in understanding its role in dormancy and relapse of microscopic metastases. Preliminary data suggest that initial low level expression of FGF-2, primarily in myoepithelial cells of normal ducts, is markedly upregulated during ductal hyperplasia, only to be lost with malignant progression. The previously established role of FGF-2 as a morphogenic differentiation agent suggests this to be a reactive process by ductal cells during the uncontrolled proliferation of hyperplasia, an effect largely lost with malignant transformation. More samples will be stained to allow for statistically significant correlations. These data will support a role for FGF-2 expression as a differentiation agent if found in dormant malignant micrometastases in the bone marrow of patients to be stained in this project. To provide mechanistic support, the In vitro effects of FGF-2 were determined on breast cancer cell lines. FGF-2 caused a large reduction of well-differentiated breast cancer cells, inhibited clonogenicity in tissue culture and caused massive upregulation of integrin alpha5 expression. The ligation of integrin alpha5 by fibronectin specifically provided survival signaling and partly restored clonogenicity to the non-growing cells. These experiments provide a paradigm for dormancy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408702
Entities
People
- Robert Wieder