fig2

Figure 2. Signal transduction pathways differentially regulated by E₂ and tamoxifen in tamoxifen-resistant model. E₂ and tamoxifen (TAM) exert differential functions on nuclear estrogen receptor α (ERα). E₂ activates classical ER-target genes but TAM acts to block gene activation. Both E₂ and TAM increase the non-genomic activity of ERα through membrane-associated molecules such as extracellular matrix (ECM), c-Src, insulin-like growth factor-1 receptor (IGF-1R), and focal adhesion kinase (FAK) to enhance downstream signaling cascades, leading to acquired resistance^[32]