Īnestis A, Karamouzis MV, Dalagiorgou G, Papavassiliou AG (2015) Is androgen receptor targeting an emerging treatment strategy for triple negative breast cancer? Cancer Treat Rev 41:547Ĭochrane DR, Bernales S, Jacobsen BM et al (2014) Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Īleskandarany MA, Rakha EA, Ahmed MA et al (2011) Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer. Moreover, ER β expression may identify a new subset of TNBC that would respond more favorable to anti-androgens.Īkaza H, Hinotsu S, Usami M et al (2009) Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. ConclusionsĬollectively, our results provide evidence for a novel mechanism by which ER β exerts oncosuppressive effect in AR-positive TBNC through direct and indirect interactions with AR. The administration of enzalutamide enhanced AR:ER β heterodimers formation increasing the anti-tumor capacity of ER β. ER β expression increased the sensitivity of MDA-MB 453 cells to anti-androgens and especially to enzalutamide. Enzalutamide is a more potent anti-androgen in AR + TNBC compared to bicalutamide. Directly, ER β formed heterodimers with AR in MDA-MB 453 cells and in human tissue samples impeding AR from forming homodimers. Indirectly, ER β decreased AR activation through the inhibition of PI3K/AKT signaling pathway. ER β expression reversed the aggravating role of AR in both indirect and direct ways. Transient transfection of ER β in MDA-MB 453 AR-positive TNBC cell line significantly inhibited cell proliferation, metastatic potential and induced apoptosis. Receptors’ localization was detected by immunofluorescence and their physical association was examined using proximity ligation assay (PLA), which enables the visualization of interacting proteins in fixed cells and tissues. Protein levels of involved molecules were assessed using Western blot. MethodsĮR β expression was examined in AR-positive TNBC cell line using MTT assay, scratch and Annexin V-FITC assay in the presence or absence of anti-androgens. We evaluated the impact of ER β expression along with anti-AR drugs in AR-positive TNBC. Androgen receptor (AR) is playing an important role in the progression of a subset of TNBC.
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