We showed, by overexpressing the androgen receptor in neuroblastoma cells SH-SY5Y or knocking it down in human neural stem cells, that this regulation involves the androgen receptor.
<b>Conclusion:</b> Our results suggested that androgen receptor may involve in the progression of neuroblastoma as well as provided insight into a new target for the diagnosis and treatment of neuroblastoma patients.
To shed light on these unique aspects of this tumor, we investigated the clonality of neuroblastomas by analyzing the inactivation patterns through methylation of the human androgen receptor gene on the X chromosomes in female patients.
Pre-treatment of mouse neuroblastoma Neuro2a cells expressing an AR with 51 glutamine residues with 10 microM 17beta- or 17alpha-estradiol prevented induction of AR aggregation by testosterone.
To examine the mechanisms by which these expanded repeat ARs (Exp-ARs) are toxic to neurons, we have established and characterized a cell culture model by stably transfecting SH-SY 5Y neuroblastoma cells with cDNAs containing either normal AR (81 series; 23 Glns) or Exp-AR (902 series; 56 Glns).
To understand further the mechanisms that lead to neuronal cell death in SBMA, we generated SHSY5Y neuroblastoma cell lines that stably express identical levels of wild-type (19 polyglutamine repeat) or SBMA (52 polyglutamine repeat) androgen receptor.
In order to investigate the properties of the SBMA androgen receptor in neuronal cells, cDNAs coding for a wild-type (19 CAG repeats) and a SBMA mutant androgen receptor (52 CAG repeats) were transfected into mouse neuroblastoma NB2a/d1 cells.