The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism

We explored whether modulation of the estrogen receptor (ER) signaling is possible through an aryl hydrocarbon receptor nuclear translocator (Arnt)-dependent mechanism. We utilized the Arnt-interacting protein 2 (Ainp2) to examine whether the presence of Ainp2 in MCF-7 cells would interfere with the Arnt-mediated ER signaling. We found that Arnt increased the 17 beta-estradiol (E2)-dependent luciferase activity and Ainp2 significantly suppressed this Arnt-mediated luciferase activity. Ainp2 significantly suppressed 25% of the E2- and Arnt-dependent up-regulation of the GREB1 message. No suppression of the ER target gene expression by Ainp2 was detected in Arnt-knockdown MCF-7 cells and in Arnt-independent ER signaling. Although Ainp2 did not interact with ER alpha and ER beta, it suppressed the ER alpha::Arnt interaction and reduced the E2-driven recruitment of Arnt to the GREB1 promoter. We concluded that Ainp2 suppresses the ER signaling by not allowing Arnt to participate in the ER-dependent, Arnt-mediated activation of gene transcription.