ESR1 and breast cancer: In vitro investigations using different human breast cancer cell lines demonstrated the reduction of AKT activation by celecoxib or Ly117018 treatment.68–70 Increased activation of AKT was shown to result in an increased estrogen receptor alpha activation, which was also attributed for causing resistance to tamoxifen.71 Constitutively, increased AKT activation resulted in an upregulation of COX-2 protein.72 Thus, the interaction of the ER- and the COX 2-signalling pathways are of further interest.