Figure 10.

A model of EGF/EGFR-induced inhibition of a Luminal-A phenotype in MCF-7 cells. MCF-7 breast cancer cells are of a Luminal-A phenotype, express ERα and PGR, and are negative for HER2 amplification. The activity of miR-206 can influence this phenotype through the direct targeting and repression of not only ERα, but of coactivators (SRC-1 and SRC-3) and transcription factors (GATA-3) that are required to mediate estrogenic responses within this cell type. The expression and activity of miR-206 are enhanced by active EGF/EGFR signaling, a hyperactive signaling pathway found in a majority of ERα-negative Basal-like breast tumors. This supports the notion that ERα-positive tumors acquiring ancillary EGFR signaling would have enhanced miR-206 levels, which would push the bi-stable system within the tumor from an ERα-positive to an ERα-negative phenotype. Also, given that EGFR expression induces a Basal-like gene expression pattern in MCF-7 cells (12), miR-206 may also actively promote a Basal-like phenotype.