EGFR-Dependent Regulation of Matrix-Independent Epithelial Cell Survival
Annual rept. 15 Mar 2003-14 Mar 2004
THOMAS JEFFERSON UNIV PHILADELPHIA PA
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Background Signaling through the epidermal growth factor receptor EGFR has been implicated in both effective wound healing and epithelial neoplasia. We have identified a novel function of the EGFR in support of epithelial cell survival, particularly in conditions of anchorage-independence. Furthermore, we have implicated MEKMAPK signaling in this process. Objectivehypothesis Define molecular mechanisms and pathways by which EGFR activation supports epithelial cell survival. Two specific aims focus on 1 post translational modification of relevant Bcl-2 family members by EGFR activation through MAPK-dependent mechanisms and, 2 STAT3 activation by deregulated EGFR signaling as observed in epithelial cancer. Progress During the last funding period we have focused on modification of Bcl-2 family members during suspension culture. Specifically, we have characterized the pro-apoptotic Bcl-2 family member BIM to be upregnlated during suspension culture and, potentially, phosphorylated by EGFR activation. These results are very encouraging and will be pursued further. The studies proposed under Specific Aim 2 have been completed and have been accepted for publication.
- Anatomy and Physiology
- Medicine and Medical Research