EGFR-Dependent Regulation of Matrix-Independent Epithelial Cell Survival
Annual rept. 15 Mar 2002-14 Mar 2005
THOMAS JEFFERSON UNIV PHILADELPHIA PA
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Signaling through the epidermal growth factor 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 posttranslational 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 funding period from March, 2004 to March, 2005 we have completed a study on posttranslational modification of BIM, a pro-apoptotic family member of the Bcl-2 family through ERKMAPK. This work is relevant to SA1 of the original application and has been submitted and is currently being revised to be published in Oncogene. In addition, we have further characterized signaling through the MAPKinases JNK and p38 as it relates to- EGFR activation in the anchorage-independent state.
- Anatomy and Physiology
- Medicine and Medical Research