DTIC ADA504024: Effect of MUC1 Expression on pdf

DTIC ADA504024: Effect of MUC1 Expression on

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In previous years of this project (2006-2008); we have identified a novel mechanism of internalization and trafficking for the epidermal growth factor receptor in breast cancer cells that overexpress the MUC1 oncoprotein (El Bejjani et al 2006). Additionally, I showed that in the presence of MUC1, EGFR is trafficked to the endocytic recycling compartment and not to the late endosome. This provides an explanation for the decrease in EGFR degradation and increase in signaling observed in MUC1-expressing breast cancer cells. Additionally, I identified a novel non-canonical EGFR trafficking mechanism in MUC1 overexpressing breast cancer cells. I show that following EGF-induced internalization, EGFR is trafficked to the early endosome regardless of MUC1 expression. Interestingly, in later time points, we observed that EGFR is colocalized with late endosomal markers only when MUC1 expression is knocked down with siRNA. In cells that express high levels of MUC1 protein, I observed a colocalization of MUC1 and EGFR at the endocytic recycling compartment (ERC) and not at the late endosome.

Furthermore, I showed that localization of EGFR to the ERC affects EGFR signaling through the pSTAT3 pathway but not through the pAKT or dpERK pathways. These results consists a major part of a publication still in preparation in Dr Joyce Schroeder’s lab which will be submitted after my graduation

• Creator/s: Defense Technical Information Center
• Date: 4/1/2009
• Year: 2009
• Book Topics/Themes: DTIC Archive, , ARIZONA UNIV TUCSON, *BREAST CANCER, *PHOSPHORYLATION, *RECEPTOR SITES(PHYSIOLOGY), SENSE ORGANS, APOPTOSIS, TYROSINE, GROWTH(PHYSIOLOGY), CELLS(BIOLOGY), DEGRADATION, MEMBRANES(BIOLOGY), EPIDERMIS

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