ESR1 and breast cancer: It should be mentioned that there might be several, not necessarily mutually exclusive mechanisms by which Gab2 is up-regulated in breast cancer such as the amplification of the GAB2 locus on 11q13-14 [35], a region commonly amplified in breast cancers, the aberrant activity of the E2F transcription factor [162,206], which is often dys-regulated in tumours and binds directly to the human GAB2 promoter, and aberrant estrogen receptor (ER) signalling [163].