The estrogen receptor beta agonist diarylpropionitrile (DPN) inhibits medulloblastoma development via anti-proliferative and pro-apototic pathways

Gender-related differences in medulloblastoma (MB) development have been reported with a higher incidence in males (slightly above 60%) than in females, female gender being also a significantly favorable prognostic factor in MB. The present study focused on the evaluation of the mechanisms by which estrogens protect against MB formation. To this end, we used a well characterized mouse model of MB - the Patched1 heterozygous mice. Ovariectomized mice were treated with 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), a highly potent ER beta agonist, or 4,4',4 ''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), a highly potent ER alpha agonist. Our results show that the ER beta selective agonist DPN significantly inhibits development of MB preneoplastic lesions when compared with untreated ovariectomized mice, restoring the final incidence to that observed in the intact controls, and that these effects were achieved via activation of anti-proliferative and pro-apototic pathways. On the other hand, the ER alpha selective agonist PPT did not influence MB tumorigenesis relative to untreated ovariectomized mice. (C) 2011 Elsevier Ireland Ltd. All rights reserved.