Evidence indicates that lipid metabolites may play a role in breast cancer. Some data support a role for linoleic acid metabolism while other more recent data indicate the over-expression of PGHS-2 in human breast tumors. No expression of PGHS-2 was observed in normal human breast tissue. The EGFR and the oncogene erb-2 play and important role in breast cancer. Since SHE cells represent a model system for studying the interactions of lipids with the EGFR signaling pathway, we examined how the presence of erb-2 would alter lipid metabolism. We transfected normal SHE fibroblasts with plasmid DNA vectors containing retroviral v-erbB oncogene or its cellular homolog c-erbB-2 and established stable transfected cell lines. erbB-Transfected cells demonstrate increased lipoxygenase metabolism of both linoleic and arachidonic acid. We have examined the metabolism of linoleic and arachidonic acid in a variety of human breast carcinoma cell lines which vary in their expression of EGF receptor, c-erbB2/HER2, and estrogen receptor. We have observed a close association between high levels of c-erbB-2 and EGF receptor expression and the extent of linoleic acid metabolism in these cells. Inhibition of lipoxygenase metabolism attenuates DNA synthesis in the erbB-2/EGFR pathaway in human breast cells and how lipid metabolites can alter EGFR-dependent phosphorylation events.
