Analysis of Signaling Pathways Involved in Tumor Promoting Functions of TGFbeta in Breast Cancer
Abstract
Transforming growth factor-Beta (TGFbeta) is an important regulator of tumor growth and metastasis formation in breast carcinomas. TGFbeta has a dual role in tumor progression, initially acting as a tumor suppressor by inhibiting the proliferation of normal epithelial cells and early stage tumor cells, and in later stages of the disease acting as a tumor promoter by inducing a more invasive tumor cell phenotype with elevated metastatic potential. This phenotypic change is often correlated with an epithelial-mesenchymal transition (EMT). The molecular basis for the switch in tumor cell responsiveness to TGFbeta is mostly unclear. The importance of the Smad signaling pathway in mediating the growth inhibitory response to TGFbeta in normal epithelial cells is well established. However, the TGFbeta signaling events leading to EMT and enhanced tumorigenic properties are poorly understood. The aims of this project are to analyze these signaling events, and to identify novel signaling molecules that interact with TGFbeta receptor complexes in invasive breast carcinoma cells. We have generated cell lines expressing different forms of the TGFbeta receptor that are now being characterized and used for the isolation of receptor complexes from the plasma membrane. Preliminary data indicate the feasibility of this approach and identify candidate receptor interacting polypeptides.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2002
- Accession Number
- ADB282213
Entities
People
- Marcus D. Kretzschmar
Organizations
- Icahn School of Medicine at Mount Sinai