In our orthotopic lung cancer model, ERβ agonist diarylpropionitrile (DPN) significantly promoted mediastinal metastasis as evidenced by in vivo imaging (Fig. 8A) and increased mediastinal lymph node size (Fig. 8B, E), whereas ERβ antagonist 4-[2-Phenyl-5,7-bis (trifluoromethyl) pyrazolo [1,5-a]-pyrimidin-3-yl] phenol (PHTPP) effectively counteracted these effects. This evidence concerns the gene ESR2 and lung cancer.