Arylamine N-acetyltransferase 1 gene regulation by androgens requires a conserved heat shock element for heat shock...

Human arylamine N-acetyltransferase 1 (NAT1) is a widely distributed protein that has been implicated in a number of different cancers including breast and prostate. Previously, NAT1 gene expression was shown to be androgen dependent, although the effect of androgens was not due to direct activation of the NAT1 promoter. Here, we show that heat shock factor (HSF)1 is induced by androgen in androgen receptor-positive prostate 22Rv1 cells. It also binds to a heat shock element (HSE) in the NAT1 promoter located 776 bp upstream of the transcriptional start site. Mutation of the HSE inhibited androgen responsiveness and prevented direct upregulation of the NAT1 promoter by HSF1. Although HSF2 also bound to the HSE, it did not increase promoter activity. HSF1 induced endogenous NAT1 activity in this cell line in the absence of androgen. This could be attenuated by pretreating cells with HSF1-directed small interfering RNA but not by a scrambled sequence. Our results show that HSF1 is an important transcription factor for induction of NAT1 in human cells and is required for androgen activation of the NAT1 promoter.