Estrogen receptor-mediated cross-talk with growth factor signaling pathways.
Estrogen (E2) palys critical roles in the development of tumors in female reproductive organs. Development of most breast cancers is dependent on E&sub2; in most cases. Most E&sub2; actions are considered to be exerted through two subtypes of Estrogen receptors (ERs), ERalpha and ERbeta. 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 E&sub2;, 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 (Kato et al, 1995). Furthermore, we have identified a coactivator that specifically interacts with ER alpha AF-1 (Endoh et al, 1999). In this review, this cross-talk is discussed in terms of the transactivation function of ERs and their coactivators.
Kato
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The Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
D000818:Animals; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D006133:Growth Substances; D011960:Receptors, Estrogen; D020928:Mitogen-Activated Protein Kinases