In assessing the mechanism by which E2-ERα mediates the CXXC5 gene expression in a cell model derived from breast adenocarcinoma, we show here that E2-ERα regulates the transcription of CXXC5 by a direct interaction with an ERE sequence present at a region upstream of the initial translation codon of the CXXC5 locus. Here, ESR1 is linked to breast adenocarcinoma.