SIM2 and ductal breast carcinoma in situ: Based on our previous results reporting a role for COX-2 in promotion of DCIS invasion [22], and results showing that SIM2 is lost in IDC compared with DCIS in patient samples [39, 50], we predict that loss of SIM2s may be important for progression of in situ lesions to invasive disease via upregulation of COX-2 expression and activity.