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Medulloblastoma (MD) is the most common malignant brain tumor in children. These invasive neuroectodermal tumors arise from cerebellar granule cell-like precursors. In the developing cerebellum, estrogen influences growth and viability of granule cell precursors that transiently express elevated levels estrogen receptor-β (ERβ) during differentiation. Immunoanalysis revealed that ERβ was expressed in the maturing human cerebellum, in all 22 primary MD tumors analyzed, and in two MD-derived cell lines (D283Med and Daoy). Very low levels of ERα-like proteins were detected in each cell line and 41% of tumor samples. Physiological concentrations of the 17β-estradiol- or the ERβ-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile diarylpropionitrile dose-dependently increased MD growth and cellular migration. In contrast, the ERα-selective agonist (4-propyl-[1H]pyrazole-1,3,5-triyl) trisphenol did not …