Androgen receptors containing expanded polyglutamine tracts exhibit progressive toxicity when stably expressed in the neuroblastoma cell line, SH-SY 5Y
| Autor: | Michael J. McPhaul, D M Avila, D R Allman, Jean-Marc Gallo |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
0301 basic medicine
Time Factors medicine.drug_class Cell Population Immunoblotting Apoptosis Biology Transfection Binding Competitive General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Neuroblastoma 0302 clinical medicine medicine Tumor Cells Cultured Humans education Receptor Genetics Neurons education.field_of_study medicine.disease Androgen Immunohistochemistry Cell biology Androgen receptor Spinal and bulbar muscular atrophy 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence Receptors Androgen 030220 oncology & carcinogenesis Peptides Trinucleotide Repeat Expansion Intracellular |
| Zdroj: | Europe PubMed Central King's College London |
| ISSN: | 1535-3702 |
| Popis: | The pathogenesis of X-linked spinal and bulbar muscular atrophy (SBMA) has been traced to an expansion of repeated glutamine (Gin) residues within the amino terminus of the human androgen receptor (AR). 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 Gins) or Exp-AR (902 series; 56 Gins). At a low passage number, no differences in cell morphology, growth properties, or susceptibility to toxic insults were observed between clones expressing normal AR or Exp-AR. Initially, both types of cultures were found to express similar levels of specific hormone binding in monoiayer binding assays. Immunohistochemical studies demonstrated the vast majority of both the normal AR and Exp-AR were localized to the nucleus in the absence and presence of androgen. As the 902 series of clones were propagated, the Exp-AR content in the cells appeared to decline progressively. However, this decrease actually reflects a gradual disappearance of the Exp-AR cell population. No such selection occurred during the propagation of cells expressing the normal AR. This selection against cells expressing physiological levels of Exp-AR occurs in the absence of intracellular aggregates and suggests that mechanisms other than those Involving the formation of aggregates underlie the observed toxicity of Exp-ARs. |
| Databáze: | OpenAIRE |
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