Metastatic Progression of Breast Cancer by Allelic Loss on Chromosome 18q21
Abstract
The molecular basis of a pro-oncogenic role of TGFbeta in promoting advanced metastatic cancer remains unclear. The TGFbeta levels are increased locally and systemically in-advanced breast tumors particularly at the leading edges and in metastasis. Our studies provide direct evidence for the association between the inactivation of SMAD4 gene localized to chromosome 18q and upregulation of pro-angiogenic/ metastatic factors such as angiopoietin and VEGF in breast cancer. Additionally, our preliminary data also provides evidence for the synergistic activation of pro-angiogenic/ metastatic effects by TGFbeta in the presence of defective SMAD4 in breast cancer. We therefore hypothesize that normal Smad4 mediated events are required to maintain suppression of metastasis and disabling these events is a major step towards the development of metastatic malignant breast cancer. We are in the process of the identification and characterization of the mediator and effector genes that regulate metastatic progression of breast cancer upon inactivation of the Smad4 mediated events.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA430065
Entities
People
- Sam Thiagalingam
Organizations
- Boston University