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Protective role of 17 β-estradiol on medulloblastoma development in Patched 1 heterozygous mice

TitleProtective role of 17 β-estradiol on medulloblastoma development in Patched 1 heterozygous mice
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2010
AuthorsMancuso, Mariateresa, Leonardi Simona, Ceccarelli Manuela, Pasquali Emanuela, De Stefano Ilaria, Prisco Maria Grazia, Rebessi Simonetta, Tanori Mirella, Scambia Giovanni, Di Majo Vincenzo, Pazzaglia Simonetta, Saran Anna, and Gallo Daniela
JournalInt J Cancer
Volume127
Issue12
Pagination2749-57
Date Published2010 Dec 15
ISSN10970215
KeywordsAnimals, Blotting, Western, Cerebellar Neoplasms, estradiol, estrogen receptor beta, Estrogens, Female, heterozygote, Immunoenzyme Techniques, Insulin-Like Growth Factor I, medulloblastoma, Mice, Mice, Knockout, ovariectomy, patched receptors, Patched-1 Receptor, Receptors, Cell Surface, Receptors, Estrogen, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Whole-Body Irradiation
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.

DOI10.1002/ijc.25293
Alternate JournalInt. J. Cancer
Citation Key5068
PubMed ID21351254