Role of Epidermal Growth Factor Receptors and Their Ligands in Normal Mammary Epithelial and Breast Cancer Cells
Abstract
Epidermal growth factor (EGF) and transforming growth factor a (TGFalpha) acting through EGF receptors (EGFR) regulate the development of normal mammary epithelial cells (MEC) and breast cancer. Primary culture studies examined the effects of EGF and TGFalpha in MEC. PD158780, a selective inhibitor of the tyrosine kinase domain of EGFR, helped demonstrate that EGFR signaling was required for the proliferation and functional differentiation of immature MEC from days 0-7 of culture, and survival of terminally differentiated MEC from days 17.5-21 of the study. EGFR levels were expressed at high levels in non-functional MEC and MEC undergoing apoptosis whereas functionally differentiated MEC expressed relatively low levels of EGFR. In EGF medium, cultured MEC expressed peak levels of erbB2 and erbB3 from day 7-14 of culture, whereas erbB4 levels were only detected within MEC cultured for 7 and 10.5 days. MEC isolated from mammary glands expressed high levels of erbB2 and erbB3 in virgin rats and rats during pregnancy and involution, and relatively low levels during lactation, whereas erbB4 appeared to be uniformly expressed throughout the developmental stages analyzed. These findings will help in the development of therapies to treat aggressive human breast cancers that often overexpress EGFR and/or other erbB receptors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADB232305
Entities
People
- Kathleen M Darcy
Organizations
- Health Research, Incorporated