ANDROGEN-CONTROLLED SPECIFIC GENE-EXPRESSION IN NEUROBLASTOMA-CELLS

In Kennedy's syndrome, a mutation in the androgen receptor (AR) gene leads to sensory and lower motor neurone degeneration, therefore genes that are regulated by androgens in neurones may be important in the process of motor neurone cell death. The aim of this study was to identify androgen-inducible genes in the human neuroblastoma cell line SH-SY5Y. We have shown that SH-SY5Y cells expressed the AR by Northern blot analysis using a P-32-labelled probe derived from a human AR cDNA. Differential display of mRNAs has been used to identify and clone putative genes that are regulated by androgens in SH-SY5Y cells. Nine cDNA fragments, ranging in size from 180 bp to 480 bp, corresponding to mRNA species which appear to be differentially expressed in response to 5 alpha dihydrotestosterone (DHT), have been successfully cloned. These are now being sequenced and used as hybridisation probes for Northern blot analysis in order to confirm their induction by DHT. Characterisation of these genes may provide clues to the mechanisms of motor neurone degeneration.