Alteration of EGFR family members through targeting lipid raft signaling
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Epidermal Growth Factor Receptors (EGFR) comprise a family of proteins that are overexpressed in more than 30% of breast cancers. These transmembrane receptors localize to specialized plasma membrane domain called lipid rafts, highly ordered domains enriched in cholesterol and glycophosphingolipids. In contrast to most lipid raft associated receptors, whose signaling is stimulated by the aggregation of lipid rafts to form signaling platforms, EGFR signaling is associated with movement of EGFR out of the lipid raft. Therefore, EGFR signaling can be potentially modulated by targeting lipid rafts, through alteration of structure or fluidity. The purpose of the present study is to test the hypothesis that conjugated linoleic acid (CLA), a dietary fatty acid which inhibits breast cancer, mediates some of its effects through alteration of raft dynamics. The effects of CLA on breast cancer cell lipid raft structure were examined by staining with fluorescent cholera toxin B subunit, which binds specifically to lipid rafts. The results do not indicate a consistent increase or decrease of lipid raft size or raft count per cell on CLA and EGF treatment in replicate experiments. They also do not consistently change the expression of EGFR and pEGFR. Although colocalization studies were carried out, confocal microscopy will indicate stronger results for colocalization. Further studies involving western blots on cell lysates and experiments for change in downstream signaling will be carried out to effectively study the effect of CLA on breast cancer cell lines.