title: Differential regulation of apoptosis-associated genes by estrogen receptor alpha in human neuroblastoma cells.
abstract: OBJECTIVE
  The neuroendocrinology of female sex hormones is of great interest for a variety of neuropsychiatric disorders. In fact, estrogens and estrogen receptors (ERs) exert neuromodulatory and neuroprotective functions. Here we investigated potential targets of the ER subtype alpha that may mediate neuroprotection and focused on direct modulators and downstream executors of apoptosis.
  
  
  METHODS
  We employed subclones of human neuroblastoma cells (SK-N-MC) stably transfected with one of the ER subtypes, ERalpha or ERbeta. Differences between the cell lines regarding the mRNA expression levels were examined by qPCR, changes on protein levels were examined by Western Blot and immunocytochemistry. Differences concerning apoptosis induction were analysed by cell survival assays which included primary rat neurons.
  
  
  RESULTS
  In this report we show a potent protection against apoptosis-stimuli in ERalpha expressing cells compared to controls lacking ERalpha. In fact, almost a complete silencing of Caspase 3 expression in SK-ERalpha cells compared to SK-01 control transfected cells was observed. In addition, prosurvival bcl2, bag1 and bag3 expression was highly up-regulated in the presence of ERalpha.
  
  
  CONCLUSIONS
  Taken together, we identified Caspase 3, BAG1 and BAG3 as key targets of ERalpha in neuronal cells that may play a role in ERalpha-mediated neuroprotection.
authors.affiliation: Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Brendel
authors.forename: Vanessa
authors.initials: V
authors.lastname: Felzen
authors.forename: Tobias
authors.initials: T
authors.lastname: Morawe
authors.forename: Dieter
authors.initials: D
authors.lastname: Manthey
authors.forename: Christian
authors.initials: C
authors.lastname: Behl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D053148:Caspase 3