EFFECT OF ANDROGENS ON CELLULAR PROLIFERATION, DIFFERENTIATION, GLOBAL GENE EXPRESSION OF NEUROBLASTOMA CELLS AND THEIR EFFECT ON NONCODING GENE EXPRESSION IN NEUROBLASTOMA AND LYMPHOBLASTOID CELL LINES. Open Access
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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by three major symptoms including impaired social interaction and communication, aberrant language development, and repetitive, stereotyped behaviors with restricted interests. Epidemiological studies reveal that the incidence of ASD is about 4 times higher in males than in females. Previous studies have demonstrated elevated testosterone levels in the serum of autistic individuals, including females. Furthermore, dysregulation in the steroid biosynthesis pathway has been previously shown by our laboratory. We also identified 20 novel genes that were differentially expressed in 3 subtypes of autism, distinguished by severity profile of symptoms probed by the Autism Diagnostic Interview-Revised assessment instrument.In this study, steroid-treated cells were studied using DNA microarrays, realtime-qPCR and cell proliferation assays to study the effect of steroid hormones on the proliferation and differentiation of neuroblastoma cell lines as well as to discover global and specific gene expression changes caused by androgen treatment. Many interesting biological functions including nervous system development and function as well as small molecule biochemistry were found to be affected when treated with steroid hormones. Molecules like PRKCA and AChE, which affect pathways involved in neurological disease and development, were found to be differentially expressed. The steroid treatment also affected proliferation and differentiation of neuroblastoma cells. These findings show that increase in steroid hormone levels can cause changes in important pathways in the brain and peripheral systems, and that androgens, in particular, might be one of the factors involved in the etiology of autism.