Effect of ligand-activated estrogen receptor β on lymphoma growth in vitro and in vivo

Estrogen receptor β (ERβ) is expressed in immune cells and studies have suggested an antiproliferative function of ERβ. We detected ERβ expression in murine T- and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ERβ agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ERβ agonists diarylpropionitrile (DPN) and KB9520 showed a strong antiproliferative effect. When grafting mice with murine T-cell lymphoma cells, male mice developed larger tumors compared with female mice, a difference that was abolished following ovariectomy, showing estrogen-dependent growth in vivo. To investigate whether lymphoma growth may be inhibited in vivo by ERβ agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ERβ-selective agonists strongly inhibited lymphoma growth. The reduced tumor size seen following either DPN or KB9520 treatment was due to reduced proliferation and increased apoptosis. Our results show an ERβ ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ERβ and that lymphoma cell growth in vivo can efficiently be inhibited by ERβ agonists. This suggests that ERβ agonists may be useful in the treatment of lymphomas.