title: Protective role of 17 β-estradiol on medulloblastoma development in Patched 1 heterozygous mice.
abstract: Medulloblastoma (MB) is the most common pediatric tumor of the CNS, representing ∼20% of all childhood CNS tumors. Although in recent years many molecular mechanisms that control MB development have been clarified, the effects of biological factors such as sex on this tumor remain to be explained. Epidemiological data, in fact, indicate a significant difference in the incidence of MB between the 2 sexes, with considerably higher susceptibility of males than females. Besides this different susceptibility, female sex is also a significant favorable prognostic factor in MB, with girls having a much better outcome. Despite these literature data, there has been little investigation into estrogen influence on MB development. In our study, we evaluated how hormone deficiency resulting from ovariectomy and hormone replacement influences the development of early and advanced MB stages in Patched1 heterozygous mice, a well-characterized mouse model of radiation-induced MB. Susceptibility to MB development was significantly increased in ovariectomized Ptch1(+/-) females and restored to levels observed in control mice after estrogen replacement. We next investigated the molecular mechanisms by which estrogen might influence tumor progression and show that ERβ, but not ERα, is involved in modulation of MB development by estrogens. Finally, our study shows that a functional interaction between estrogen- and IGF-I-mediated pathways may be responsible for the effects observed.
authors.affiliation: Section of Toxicology and Biomedical Sciences, Research Center Casaccia, ENEA, 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: Manuela
authors.initials: M
authors.lastname: Ceccarelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pasquali
authors.forename: Ilaria
authors.initials: I
authors.lastname: De Stefano
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Prisco
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rebessi
authors.forename: Mirella
authors.initials: M
authors.lastname: Tanori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di 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; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004958:Estradiol / Q000627:therapeutic use*; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006579:Heterozygote; D007124:Immunoenzyme Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008527:Medulloblastoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000502:physiology*; D011960:Receptors, Estrogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014916:Whole-Body Irradiation
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I