Collaboration of AR and ERα in conferring resistance to an aromatase inhibitor.

579 Background: We have previously shown a role for AR overexpression in tamoxifen resistance in ERα-positive MCF-7 breast cancer cells; here we hypothesized that AR overexpression might similarly be involved in resistance to the aromatase inhibitor anastrazole (Anas). Methods: MCF-7 cells were transfected to express the aromatase gene (MCF-7 Arom), or the aromatase and AR (MCF-7 AR Arom cells). Western blot analysis was used to evaluate protein levels, MTT and soft agar assays to evaluate proliferation, luciferase reporter assays to evaluate transcriptional activities and confocal microscopy was used for localization. Results: Anas inhibited androstendione (AD)-stimulated growth in MCF-7 Arom cells but not in MCF-7 AR Arom cells. Similarly, Anas did not inhibit ERα transcriptional activity in MCF-7 AR Arom cells. Enhanced activation of pIGF-1R, pIRS-1, pAKT, and pMAPK were also observed in AR Arom cells, suggesting constitutive activation of nongenomic signaling in these cells. Consistent with activation...