title: The estrogen receptor beta agonist diarylpropionitrile (DPN) inhibits medulloblastoma development via anti-proliferative and pro-apototic pathways.
abstract: 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 ERβ agonist, or 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), a highly potent ERα agonist. Our results show that the ERβ 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 ERα selective agonist PPT did not influence MB tumorigenesis relative to untreated ovariectomized mice.
authors.affiliation: Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile CR-Casaccia, Rome, Italy. mariateresa.mancuso@enea.it
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Mancuso
authors.forename: Simona
authors.initials: S
authors.lastname: Leonardi
authors.forename: Paola
authors.initials: P
authors.lastname: Giardullo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasquali
authors.forename: Fabiana
authors.initials: F
authors.lastname: Borra
authors.forename: Ilaria De
authors.initials: ID
authors.lastname: Stefano
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Prisco
authors.forename: Mirella
authors.initials: M
authors.lastname: Tanori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Vincenzo Di
authors.initials: VD
authors.lastname: Majo
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.forename: Daniela
authors.initials: D
authors.lastname: Gallo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D047629:Estrogen Receptor beta / Q000819:agonists*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008527:Medulloblastoma / Q000473:pathology*; D051379:Mice; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D047629:Estrogen Receptor beta; D009570:Nitriles; D011422:Propionates