Protective role of 17β-estradiol on medulloblastoma development in Patched1 heterozygous mice

Mariateresa Mancuso, Simona Leonardi, Manuela Ceccarelli, Emanuela Pasquali, Ilaria De Stefano, Maria Grazia Prisco, Simonetta Rebessi, Mirella Tanori, Giovanni Scambia, Vincenzo Di Majo, Simonetta Pazzaglia, Anna Saran, Daniela Gallo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2749-2757
Number of pages9
JournalInternational Journal of Cancer
Volume127
Issue number12
DOIs
Publication statusPublished - Dec 15 2010

Keywords

  • ERα
  • ERβ
  • IGF-I
  • Ptch1
  • Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Mancuso, M., Leonardi, S., Ceccarelli, M., Pasquali, E., Stefano, I. D., Prisco, M. G., Rebessi, S., Tanori, M., Scambia, G., Majo, V. D., Pazzaglia, S., Saran, A., & Gallo, D. (2010). Protective role of 17β-estradiol on medulloblastoma development in Patched1 heterozygous mice. International Journal of Cancer, 127(12), 2749-2757. https://doi.org/10.1002/ijc.25293