Drivers and suppressors of triple-negative breast cancer

TNBC patient-derived xenografts in mice and found that the ERβ agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERβ is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERβ functionless on genes involved in proliferation and inflammation.