PMID- 19008315
OWN - NLM
STAT- MEDLINE
DCOM- 20090324
LR  - 20211020
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 3
DP  - 2009 Mar
TI  - Blockade of estrogen receptor signaling inhibits growth and migration of 
      medulloblastoma.
PG  - 1112-21
LID - 10.1210/en.2008-1363 [doi]
AB  - 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-beta (ERbeta) during differentiation. Immunoanalysis revealed 
      that ERbeta 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 ERalpha-like proteins were detected in each cell line and 41% of tumor 
      samples. Physiological concentrations of the 17beta-estradiol- or the 
      ERbeta-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile 
      diarylpropionitrile dose-dependently increased MD growth and cellular migration. 
      In contrast, the ERalpha-selective agonist (4-propyl-[1H]pyrazole-1,3,5-triyl) 
      trisphenol did not influence MD growth. Similar to previous studies in normal 
      cerebellar granule cell precursors, these studies demonstrate that the 
      physiological actions of estrogens in MD are mediated by ERbeta. Preclinical 
      studies assessing the therapeutic efficacy of antiestrogen chemotherapeutics for 
      treating human MD were performed. It was found that pharmacological inhibition of 
      ER-mediated signaling with the ER antagonist drug Faslodex (ICI182,780) blocked 
      all estrogen-mediated effects in both cell culture and xenograft models of human 
      MD. These studies have revealed that functional ERbeta expression is a 
      fundamental aspect of MD biology and has defined antiestrogen therapy as a 
      potentially efficacious clinical approach to improve the long-term outcomes for 
      MD patients.
FAU - Belcher, Scott M
AU  - Belcher SM
AD  - Department of Pharmacology and Cell Biophysics University of Cincinnati College 
      of Medicine, Cincinnati, Ohio 45267-0575, USA. scott.belcher@uc.edu
FAU - Ma, Xiaolan
AU  - Ma X
FAU - Le, Hoa H
AU  - Le HH
LA  - eng
GR  - P30 ES006096/ES/NIEHS NIH HHS/United States
GR  - R01 ES015145/ES/NIEHS NIH HHS/United States
GR  - P30-ES06096/ES/NIEHS NIH HHS/United States
GR  - R01-ES015145/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081113
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Receptors, Estrogen)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Adolescent
MH  - Animals
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Cerebellar Neoplasms/genetics/metabolism/*pathology
MH  - Child
MH  - Child, Preschool
MH  - Down-Regulation/drug effects
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/*pharmacology
MH  - Female
MH  - Fulvestrant
MH  - Humans
MH  - Infant
MH  - Male
MH  - Medulloblastoma/genetics/metabolism/*pathology
MH  - Mice
MH  - Mice, Nude
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Estrogen/*antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Xenograft Model Antitumor Assays
PMC - PMC2654749
EDAT- 2008/11/15 09:00
MHDA- 2009/03/25 09:00
PMCR- 2010/03/01
CRDT- 2008/11/15 09:00
PHST- 2008/11/15 09:00 [pubmed]
PHST- 2009/03/25 09:00 [medline]
PHST- 2008/11/15 09:00 [entrez]
PHST- 2010/03/01 00:00 [pmc-release]
AID - en.2008-1363 [pii]
AID - 4618 [pii]
AID - 10.1210/en.2008-1363 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Mar;150(3):1112-21. doi: 10.1210/en.2008-1363. Epub 2008 Nov 
      13.