Quantitative studies of EGFR autocrine induced cell signaling and migration

Epidermal growth factor (EGF) receptor autocrine and/or paracrine signaling plays an important role in normal epithelial cell proliferation, survival, adhesion and migration. Aberrant expression of the EGF receptor and its cognate ligands have been implicated in various types of cancers, hence EGF receptor autocrine activation is thought to also be involved in tumorigenesis. EGF family ligands are synthesized as membrane-anchored proteins requiring proteolytic release to form the mature soluble, receptor-binding factor. Despite the pathophysiological importance of autocrine systems, how protease-mediated ligand release quantitatively influences receptor-mediated signaling and consequent cell behavior is poorly understood. Therefore, we explored the relationship between autocrine EGF release rate and receptor-mediated ERK activation and migration in human mammary epithelial cells. A quantitative spectrum of EGF release rates was achieved using chimeric EGF ligand precursors modulated by the addition of the metalloprotease inhibitor batimastat. We found that ERK activation increased with increasing ligand release rates despite concomitant EGF receptor downregulation.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Joslin, Elizabeth Jane

Advisor dc:contributor.advisor

• Douglas A. Lauffenburger.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/39910

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39910