Isolation and androgen regulation of the human homeobox cDNA,NKX3.1

BACKGROUND: The prostate is dependent on androgens for development and maintenance of its differentiated phenotype. We have applied the technique of differential display PCR to the androgen-sensitive prostate cancer cell line LNCaP to isolate androgen-responsive genes. METHODS: The technique of DD-PCR was applied to androgen-stimulated LNCaP cell RNA to detect and isolate androgen-responsive genes. RESULTS: The human homeobox gene NKX3.1, the homologue to mouse Nkx3.1, recently isolated by Beiberich et al. J Biol Chem 1996;271:31779-31782, was detected and cloned. NKX3.1 is induced by androgens in a time- and concentration-dependent manner. NKX3.1 is induced 6- to 7-fold in 12 hr, with a significant induction seen in 2 hr. This regulation is at the level of transcription, as androgens increase the number of new NKX3.1 transcripts, and de novo protein synthesis is not required. In humans, NKX3.1 is expressed most highly in the prostate, with a much lower level of expression seen in the testis. No other tissue examined showed detectable levels of NKX3.1 expression. CONCLUSIONS: NKX3.1 is an androgen-regulated, prostate-specific homeobox gene. We hypothesize that it may play a role in the development and differentiation of the prostate.