TI - Estrogen receptor -mediated cross-talk with growth factor signaling pathways . AB - Estrogen ( E2 ) palys critical roles in the development of tumors in female reproductive organs . Development of most breast cancers is dependent on E&amp ; sub2 ; in most cases . Most E&amp ; 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 atleast two distinct classes of coactivator complexes . In estrogen -dependent breast cancer , growth factors are shown to often act synergisticaly with E&amp ; 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 .