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

Giovanni Scambia, Silvia Leonardi, Elisabetta Pasquali, Daniela Gallo Guido, M Mancuso, P Giardullo, F Borra, Id Stefano, Mg Prisco, M Tanori, Vd Majo, S Pazzaglia, A Saran

Risultato della ricerca: Contributo in rivistaArticolo in rivista

22 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)197-202
Numero di pagine6
RivistaCancer Letters
Volume308
DOI
Stato di pubblicazionePubblicato - 2011

Keywords

  • Animals
  • Apoptosis
  • Cell Proliferation
  • Disease Models, Animal
  • Estrogen Receptor beta
  • Female
  • Immunohistochemistry
  • Male
  • Medulloblastoma
  • Mice
  • Nitriles
  • Propionates
  • Signal Transduction

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