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Estrogen receptor-mediated cross-talk with growth factor signaling pathways

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Abstract

Estrogen (E2) palys critical roles in the development of tumors in female reproductive organs. Development of most breast cancers is dependent on E2 in most cases. Most E2 actions are considered to be exerted through two subtypes of Estrogen receptors (ERs), ER α and ER β. ERs belong to the nuclear receptor superfamily, and act as ligand-inducible transcription factors to activate transcription of a particular set of the target genes. Ligand-bound ER recruits at least two distinct classes of coactivator complexes. In estrogen-dependent breast cancer, growth factors are shown to often act synergisticaly with E2, and the breast cancer often become resistant to treatment of estogen antagonists. However, the molecular basis of this coupled regulation of growth factor- and ER-mediated signaling and hormone-resistance are largely unknown. We have previously shown that MAP (mitogen-activated protein) kinase (MAPK) activated by growth factors phosphorylates and potentiates the N-terminal transactivation function (AF-1), indicating a possible molecular mechanism of a novel cross-talk between two signalings (Katoet al, 1995). Furthermore, we have identified a coactivator that specifically interacts with ER α AF-1 (Endohet al, 1999). In this review, this cross-talk is discussed in terms of the transactivation function of ERs and their coactivators.

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Kato, S. Estrogen receptor-mediated cross-talk with growth factor signaling pathways. Breast Cancer 8, 3–9 (2001). https://doi.org/10.1007/BF02967472

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