A Normal Epithelial-Mesenchymal Transition as a Model for Studying Metastatic Onset
Abstract
Genes and signaling pathways implicated in EMT and the invasiveness of breast cancers include FGF, Notch and T-box and Ets family transcription factors. Studies were performed relating to each of these pathways and factors. One aim goal was to examine the relationship between Notch signaling and the Brachyury T-box transcription factor. Through cloning and characterization of this gene it was shown that Brachyury is not a target of Notch signaling and does not function in mesoderm formation, and therefore EMT. A second T-box family member implicated in breast cancer progression, Tbx2, was cloned and characterization initiated. A polyclonal antibody was generated and antisense oligonucleotides synthesized to assay Tbx2 function during EMT. Additionally, three other T box family members were cloned; homologues of Tbx4/5, Tbx6 and T-brain/Eomes. To look at direct effectors of EMT, a series of experiments looking at members of the Rho GTPase family were initiated. Homologues of Rho, Rac and cdc42 were cloned and dominant negative/constitutively active forms of these proteins generated. The goal of this research is to provide an in vivo insight into the mechanism whereby adhesions are assembled and disassembled during BMT and metastasis and thereby identify potential targets for therapeutics aimed at preventing the spread of breast cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2001
- Accession Number
- ADA391360
Entities
People
- David R. Mcclay
- Jeffrey M. Gross
Organizations
- Duke University