Spatial Distribution of the EGF Receptor System in the Regulation of Breast Epithelial Cell Growth and Organization.
Abstract
184A1 cells do not form polarized, glandular epithelial structures when plated onto Matrigel, nor do they polarize if plated onto Transwell tissue culture inserts; therefore, 184A1 could not be used to address the primary aim of my proposal: to determine if the loss of receptor system polarization provides a growth advantage, enhances motility, or changes the differentiated state of normal cells. However, because the growth and motility of 184A1 cells require EGFR stimulation and because EGFR mis-regulation is implicated in the progression of human breast cancer, the 184A1 cell system still represents a excellent cell system in which to investigate EGFR regulation. My work has revealed that the constitutive endocytosis of the empty EGFR can be an active and specific form of EGFR spatial regulation in 184A1 cells. The process requires formation of coated pits, is specific and saturable for the EGFR and is upregulated at high cell densities. As a result of the rapid constitutive endocytosis, there is a significant increase in the proportion of receptors that can be found within the cell. Mounting evidence suggests that activated receptors initiate different signaling pathways if they are localized to vesicles as opposed to plasma membrane associated. Rapid constitutive endocytosis may provide a mechanism by which a large pool of receptors is made available to initate, preferentially, signals from internal vesicular membranes. Endocytosed ligands, or internalized, pre-activated E6FR or receptor family members could activate the internal pool of receptors either directly or in trans, respectively.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1998
- Accession Number
- ADA371384
Entities
People
- Patrick M. Burke
Organizations
- University of Utah