DAX-1 Regulation of Gene Expression in Prostate Cancer Cells

The DAX-1 gene encodes for an orphan nuclear hormone receptor which still presents undescribed interactions in cell transcriptional regulation. It derives its name from that which it has been described to be involved in namely dosage-sensitive sex reversal, adrenal hypoplasia congenita, and found in a critical region on the X chromosome, gene 1. As a nuclear receptor it is important in transcriptional regulation and has been shown to mainly act as a transcriptional repressor which identifies it as an important target for preventing cancers. Due to its role in adrenal and gonadal development and ability to interact with other nuclear receptors it is a pivotal treatment target for various cancers. Castration-resistant prostate cancers have high mortality and morbidity rates and can benefit not only from decreasing proliferation and increasing apoptotic regulators as recently described in our other works, but also from regulation of the main cause of metastasis. We have previously demonstrated that treatment of hormone responsive cancer cells with metribolone, a non-aromatizable androgen, leads to an upregulation of DAX-1 through activation of androgen receptors. Using PCR, qPCR, and Western Blot analyses, we investigate the expression of various DAX-1 targets due to the treatment provided. Targets included SLUG and TWIST, metastasis promoting factors responsible for epithelial mesenchymal transition, as well as RUNX2, a protein responsible for maintenance of bones and teeth which may have a role in prostate cancer bone metastases. Findings show that activation of androgen receptor and upregulation of DAX-1 in prostate cancer cells leads to a repression of the observed target genes such as SLUG, TWIST, and RUNX2. DAX-1 then seems to be a key component to consider for future prostate cancer research and treatments, given its ability to regulate various metastatic factors important in prostate cancer progression