TGF-Alpha Expression During Breast Tumorigenesis
Abstract
Transforming growth factor-alpha (TGFa) is an oncogenic protein that induces a transformed phenotype when overexpressed. Its receptor, Epidermal Growth Factor Receptor (EGFR), is a protooncogene that is overexpressed in breast carcinomas. This suggests that these two genes may be important contributors to breast tumorigenesis. Therefore, we examined TGFa expression in normal and transformed epithelium. We also examined TOFa and EGFR protein in human pre-invasive pathologies. Breast cancer cell lines expressed primarily the 4.6 kb TGFa transcript; no splice-variants were identified by Northern analysis. Western blot analysis showed that breast cancer cell lines expressed primarily the transmembrane form of TGFa, while freshly isolated breast tissue, tumors, epithelial organoids and early passage epithelial cultures expressed primarily the soluble form of TGFa. Due to the heterogeneity of patient samples it is difficult to determine what effect tissue culture has on normal T(3Fa protein synthesis and processing. TOFa protein expression in human archival tissue was constant during progression from benign to invasive disease. EGFR expression, however, was increased during the early hyperplasfic phase of tumor progression, suggesting that E(3FR may play a role in this pre-invasive pathology. In vitro treatment of isolated epithelial organoids with EGF and TGFa showed that TGFa was uniquely mitogenic.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB257406
Entities
People
- Kevin Taylor
Organizations
- University of Cincinnati