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

Estrogen receptor beta (ER beta) is expressed in immune cells and studies have suggested an antiproliferative function of ER beta. We detected ER beta expression in murine T-and human B-cell lymphoma cell lines and analyzed the effects of estradiol and selective ER beta agonists on lymphoma growth in culture and in vivo. Treating the cells with estradiol had minor effects on cell growth, whereas the selective ER beta 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 ER beta agonist treatment, mice grafted with murine lymphoma cells were treated with DPN or KB9520. Both ER beta-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 ER beta ligand-dependent antiproliferative effect of lymphoma cells expressing endogenous ER beta and that lymphoma cell growth in vivo can efficiently be inhibited by ER beta agonists. This suggests that ER beta agonists may be useful in the treatment of lymphomas. Leukemia (2011) 25, 1103-1110; doi:10.1038/leu.2011.68; published online 19 April 2011