“…Estrogen receptor activation modulates transcription of specific genes by engaging a number of transcription factors (co-activators or co-repressors) in target cells, which in turn negatively or positively regulate transcriptional activity of ligand-activated receptors [7,8] In addition to estrogen-mediated activation, the transcriptional effects of ERs can be mediated through several mechanisms other than estradiol (E 2 )-ER complexes binding to DNA [9,10]. It is now accepted that ERs may be activated in the absence of E 2 by a variety of extracellular signals, including growth factors [11][12][13] and other cell surface membrane-targetted signals that trigger activation of a number of kinase-regulated signaling cascades including the cAMP/protein kinase A (PKA) pathway [12,[14][15][16][17], protein kinase C (PKC) [14,18,19], phosphatidylinositol 3 (PI3)-dependent kinase (PI3-K)/Akt [20,21], and mitogenactivated protein kinase (MAPK) pathways [11,[22][23][24]. Selective expression of receptors for these ligands, along with differences in ER isoform and coactivator/corepressor protein expression allow for target cell-and promoter-specific effects of activated ERs [6,8,[25][26][27].…”